PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 19751368-1 2010 OBJECTIVE: To investigate nitric oxide (NO)-mediated changes in expression of cyclic nucleotide degrading phosphodiesterases 2A (PDE2A), PDE3B, and PDE5A in human endothelial cells. Nitric Oxide 26-38 phosphodiesterase 5A Homo sapiens 148-153 18986568-1 2008 INTRODUCTION: Endothelial dysfunction characterized by endogenous nitric oxide (NO) deficiency made 56% of patients affected with erectile dysfunction decline treatment with PDE-5 inhibitors. Nitric Oxide 66-78 phosphodiesterase 5A Homo sapiens 174-179 20101899-3 2009 Chemical inhibition of PDE5 has recently become a valid therapeutic option of nitric oxide pathway potentiation via cell cGMP availability. Nitric Oxide 78-90 phosphodiesterase 5A Homo sapiens 23-27 19222841-13 2009 CONCLUSION: Although hypoxia and ischemia play a special role in the pathogenesis of tinnitus, the PDE5-inhibitor-induced increase of nitric oxide-mediated vasodilatation exerted no specific influence on tinnitus symptomatology. Nitric Oxide 134-146 phosphodiesterase 5A Homo sapiens 99-103 19887943-11 2010 Mechanisms of action of nitric oxide/cyclic guanosine monophosphate/PDE5 pathway in the treatment of BPH/LUTS deserve further investigations. Nitric Oxide 24-36 phosphodiesterase 5A Homo sapiens 68-72 19768639-4 2009 Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. Nitric Oxide 115-127 phosphodiesterase 5A Homo sapiens 0-24 19768639-4 2009 Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. Nitric Oxide 115-127 phosphodiesterase 5A Homo sapiens 26-31 19428813-7 2009 Treatment of rats with chronic HE or hyperammonemia with inhibitors of phosphodiesterase 5 restores the function of the glutamate-nitric oxide-cGMP pathway and cGMP levels in brain as well as the ability to learn a Y maze conditional discrimination task. Nitric Oxide 130-142 phosphodiesterase 5A Homo sapiens 71-90 19638092-1 2009 BACKGROUND AND AIM: Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. Nitric Oxide 257-269 phosphodiesterase 5A Homo sapiens 134-139 18765082-3 2008 Inhibition of phosphodiesterase-5 (PDE5) is a new therapeutic strategy for overexpressing nitric oxide signaling by increasing the availability of cyclic guanosine monophosphate (cGMP). Nitric Oxide 90-102 phosphodiesterase 5A Homo sapiens 14-33 18953278-8 2008 PDE-5 inhibition with sildenafil improves cardiac output by balancing pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled nitric oxide in patients with chronic congestive heart failure and pulmonary hypertension. Nitric Oxide 168-180 phosphodiesterase 5A Homo sapiens 0-5 18765082-3 2008 Inhibition of phosphodiesterase-5 (PDE5) is a new therapeutic strategy for overexpressing nitric oxide signaling by increasing the availability of cyclic guanosine monophosphate (cGMP). Nitric Oxide 90-102 phosphodiesterase 5A Homo sapiens 35-39 16431013-4 2006 RESULTS: Chronic administration of PDE-5 inhibitors have reportedly been associated with increased persistent vascular and endothelial function--which represents a key factor in maintaining vascular tone and inducing vasodilation--by increasing the level of endothelial cGMP generated by activation of endothelial nitric oxide. Nitric Oxide 314-326 phosphodiesterase 5A Homo sapiens 35-40 17138653-13 2007 Overall, these results demonstrate that PDE5 regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling, and that vardenafil, by blocking PDE5, may be a possible therapeutic option for bladder dysfunction by ameliorating irritative lower urinary tract symptoms. Nitric Oxide 105-117 phosphodiesterase 5A Homo sapiens 40-44 17300876-3 2007 RATIONALE OF HYPOTHESIS: The presence of both Nitric Oxide Synthase and Phosphodiesterase 5 in human prostatic tissue and the effect of nitric oxide donors and PDE5 inhibitors in vitro indicate PDE5 inhibitors relax prostatic smooth muscle. Nitric Oxide 136-148 phosphodiesterase 5A Homo sapiens 194-198 17728050-11 2007 Several possible mechanisms could explain effectiveness of the PDE5-Is for treatment of PE: centrally, through the effect on the nitric oxide/cyclic guanosine monophosphate pathway; peripherally by causing relaxation of smooth muscle in the vas deferens, seminal vesicles, prostate, and urethra and inhibition of adrenergic transmission; or locally by inducing peripheral analgesia. Nitric Oxide 129-141 phosphodiesterase 5A Homo sapiens 63-67 17498710-8 2007 Fortunately, most men with ED can be successfully treated with phosphodiesterase 5A (PDE-5) inhibitors, which up-regulate the vasodilatory effects of nitric oxide (NO). Nitric Oxide 150-162 phosphodiesterase 5A Homo sapiens 63-83 17498710-8 2007 Fortunately, most men with ED can be successfully treated with phosphodiesterase 5A (PDE-5) inhibitors, which up-regulate the vasodilatory effects of nitric oxide (NO). Nitric Oxide 150-162 phosphodiesterase 5A Homo sapiens 85-90 16888683-8 2007 Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. Nitric Oxide 101-113 phosphodiesterase 5A Homo sapiens 65-69 17691956-3 2007 Chemical inhibition of PDE5 by sildenafil, tadalafil or vardenafil recently became a valid therapeutic option aimed at overexpressing the molecular pathway originated from nitric oxide and expressed via increased cell cGMP availability. Nitric Oxide 172-184 phosphodiesterase 5A Homo sapiens 23-27 17012060-4 2006 Among these agents are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), erythropoietin (EPO), and phosphodiesterase type 5 (PDE-5) inhibitors and nitric oxide (NO) donors. Nitric Oxide 167-179 phosphodiesterase 5A Homo sapiens 119-143 17012060-4 2006 Among these agents are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), erythropoietin (EPO), and phosphodiesterase type 5 (PDE-5) inhibitors and nitric oxide (NO) donors. Nitric Oxide 167-179 phosphodiesterase 5A Homo sapiens 145-150 15640438-2 2005 We now report evidence on VD expression of phosphodiesterase type 5 (PDE5), which regulates nitric oxide (NO)-induced relaxation and cGMP breakdown in smooth muscle cells. Nitric Oxide 92-104 phosphodiesterase 5A Homo sapiens 43-67 15907910-3 2005 In addition, studies on animals reveal that PDE5 inhibitors work in concert with nitric oxide and/or natriuretic peptide levels by enhancing intracellular cGMP and cGMP-mediated vasodilator effects. Nitric Oxide 81-93 phosphodiesterase 5A Homo sapiens 44-48 16498233-2 2006 The main action of sildenafil is the enhancement of the effect of nitric oxide (NO) by inhibiting the cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE-5), an enzyme responsible for degradation of cGMP. Nitric Oxide 66-78 phosphodiesterase 5A Homo sapiens 170-175 15640438-2 2005 We now report evidence on VD expression of phosphodiesterase type 5 (PDE5), which regulates nitric oxide (NO)-induced relaxation and cGMP breakdown in smooth muscle cells. Nitric Oxide 92-104 phosphodiesterase 5A Homo sapiens 69-73 15475488-2 2004 Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). Nitric Oxide 0-12 phosphodiesterase 5A Homo sapiens 146-165 16422907-0 2005 A nitric oxide-releasing PDE5 inhibitor relaxes human corpus cavernosum in the absence of endogenous nitric oxide. Nitric Oxide 2-14 phosphodiesterase 5A Homo sapiens 25-29 16422907-1 2005 INTRODUCTION: In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. Nitric Oxide 65-77 phosphodiesterase 5A Homo sapiens 140-164 16422907-1 2005 INTRODUCTION: In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. Nitric Oxide 65-77 phosphodiesterase 5A Homo sapiens 166-170 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Nitric Oxide 278-290 phosphodiesterase 5A Homo sapiens 121-125 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Nitric Oxide 278-290 phosphodiesterase 5A Homo sapiens 201-205 15475488-2 2004 Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). Nitric Oxide 0-12 phosphodiesterase 5A Homo sapiens 167-172 15223851-3 2004 Both of these Pde-5 inhibitors have vasodilating properties and effects on blood pressure (BP), and like nitrates, they work through the nitric oxide cyclic guanosine monophosphate pathway. Nitric Oxide 137-149 phosphodiesterase 5A Homo sapiens 14-19 15295092-2 2004 We hypothesized that changes in PDE5 activity might be involved in the pulmonary postnatal maturation of the nitric oxide (NO)/cGMP pathway. Nitric Oxide 109-121 phosphodiesterase 5A Homo sapiens 32-36 14551572-1 2003 Phosphodiesterase type 5 (PDE 5) is the major cGMP hydrolyzing enzyme in penile corpus cavernosum and is an important regulator of nitric oxide-mediated smooth muscle relaxation. Nitric Oxide 131-143 phosphodiesterase 5A Homo sapiens 0-24 15041473-7 2004 Nitroprusside (nitric oxide) potentiated the effect of PDE5 inhibition in elevating cGMP. Nitric Oxide 15-27 phosphodiesterase 5A Homo sapiens 55-59 15224136-2 2004 As the resulting cGMP accumulation facilitates penile smooth muscle relaxation, PDE5 inhibitors can partially reverse deficiencies in the nitric oxide (NO)/cGMP pathway to treat erectile dysfunction (ED). Nitric Oxide 138-150 phosphodiesterase 5A Homo sapiens 80-84 15066950-0 2004 Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272. Nitric Oxide 59-71 phosphodiesterase 5A Homo sapiens 14-38 14609619-4 2003 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Nitric Oxide 62-74 phosphodiesterase 5A Homo sapiens 0-19 14609619-4 2003 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Nitric Oxide 62-74 phosphodiesterase 5A Homo sapiens 21-25 14551572-1 2003 Phosphodiesterase type 5 (PDE 5) is the major cGMP hydrolyzing enzyme in penile corpus cavernosum and is an important regulator of nitric oxide-mediated smooth muscle relaxation. Nitric Oxide 131-143 phosphodiesterase 5A Homo sapiens 26-31 12789394-2 2003 Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that potentiates the nitric oxide (NO)/cGMP pathway facilitating penile smooth muscle relaxation and improving penile erection in men. Nitric Oxide 79-91 phosphodiesterase 5A Homo sapiens 42-46 12695418-9 2003 The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar. Nitric Oxide 166-178 phosphodiesterase 5A Homo sapiens 123-127 12695418-9 2003 The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar. Nitric Oxide 166-178 phosphodiesterase 5A Homo sapiens 229-233 12437503-0 2002 A Rho-kinase inhibitor, soluble guanylate cyclase activator and nitric oxide-releasing PDE5 inhibitor: novel approaches to erectile dysfunction. Nitric Oxide 64-76 phosphodiesterase 5A Homo sapiens 87-91 12437503-5 2002 Among them are Rho-kinase inhibitors, soluble guanylate cyclase activators and nitric oxide-releasing PDE5 inhibitors. Nitric Oxide 79-91 phosphodiesterase 5A Homo sapiens 102-106 12414329-2 2002 Published literature on the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway for penile erection and on PDE5 inhibition using sildenafil as the model for pharmacologic PDE5 inhibition are assessed. Nitric Oxide 28-40 phosphodiesterase 5A Homo sapiens 178-182 9916601-3 1998 Sildenafil has no direct relaxant effect on human corpus cavernosum but enhances the relaxant effect of nitric oxide (NO) on the corpus cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in this tissue. Nitric Oxide 104-116 phosphodiesterase 5A Homo sapiens 161-165 11557915-1 2001 BACKGROUND: Sildenafil, a treatment for erectile dysfunction, is a specific phosphodiesterase type 5 (PDE 5) inhibitor that enhances nitric oxide (NO)-mediated vasodilation in the corpus cavernosum by inhibiting cyclic guanosine monophosphate breakdown. Nitric Oxide 133-145 phosphodiesterase 5A Homo sapiens 76-100 11557915-1 2001 BACKGROUND: Sildenafil, a treatment for erectile dysfunction, is a specific phosphodiesterase type 5 (PDE 5) inhibitor that enhances nitric oxide (NO)-mediated vasodilation in the corpus cavernosum by inhibiting cyclic guanosine monophosphate breakdown. Nitric Oxide 133-145 phosphodiesterase 5A Homo sapiens 102-107 34471575-4 2021 Phosphodiesterase-5 (PDE-5) inhibitors act on nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and are an effective treatment option in some CPP syndromes. Nitric Oxide 46-58 phosphodiesterase 5A Homo sapiens 0-19 34471776-2 2021 Such agents would improve our understanding of the nitric oxide (NO)/cyclic guanosine 3",5"-monophosphate (cGMP)/PDE5 pathway in human pathologies and potentially lead to novel uses of PDE5 inhibitors to manage lung conditions like SARS-CoV-2-mediated pulmonary inflammatory responses. Nitric Oxide 51-63 phosphodiesterase 5A Homo sapiens 113-117 34471776-2 2021 Such agents would improve our understanding of the nitric oxide (NO)/cyclic guanosine 3",5"-monophosphate (cGMP)/PDE5 pathway in human pathologies and potentially lead to novel uses of PDE5 inhibitors to manage lung conditions like SARS-CoV-2-mediated pulmonary inflammatory responses. Nitric Oxide 51-63 phosphodiesterase 5A Homo sapiens 185-189 34369112-4 2021 More significantly, the entrapped PDE5 inhibitor (PDE5-i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Nitric Oxide 116-128 phosphodiesterase 5A Homo sapiens 34-38 34471575-4 2021 Phosphodiesterase-5 (PDE-5) inhibitors act on nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and are an effective treatment option in some CPP syndromes. Nitric Oxide 46-58 phosphodiesterase 5A Homo sapiens 21-26 33596129-9 2021 We noted reduced levels of the soluble guanylate cyclase (sGC) subunits and increased expression of the phosphodiesterase type 5A (PDE5A); conditions that affect the response to nitric oxide. Nitric Oxide 178-190 phosphodiesterase 5A Homo sapiens 104-129 33596129-9 2021 We noted reduced levels of the soluble guanylate cyclase (sGC) subunits and increased expression of the phosphodiesterase type 5A (PDE5A); conditions that affect the response to nitric oxide. Nitric Oxide 178-190 phosphodiesterase 5A Homo sapiens 131-136 33718200-5 2021 Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Nitric Oxide 124-136 phosphodiesterase 5A Homo sapiens 42-46 33670094-6 2021 The results revealed that sulfoaildenafil can affect the therapeutic level of nitric oxide through the upregulation of nitric oxide synthase and phosphodiesterase type 5 (PDE5) gene expressions. Nitric Oxide 78-90 phosphodiesterase 5A Homo sapiens 145-169 33670094-6 2021 The results revealed that sulfoaildenafil can affect the therapeutic level of nitric oxide through the upregulation of nitric oxide synthase and phosphodiesterase type 5 (PDE5) gene expressions. Nitric Oxide 78-90 phosphodiesterase 5A Homo sapiens 171-175 32526061-6 2021 OBJECTIVES: Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. Nitric Oxide 84-96 phosphodiesterase 5A Homo sapiens 109-137 33348311-1 2021 Phosphodiesterase 5 (PDE5) is one of the most well-studied phosphodiesterases (PDEs) that specifically targets cGMP typically generated by nitric oxide (NO)-mediated activation of the soluble guanylyl cyclase. Nitric Oxide 139-151 phosphodiesterase 5A Homo sapiens 0-19 33348311-1 2021 Phosphodiesterase 5 (PDE5) is one of the most well-studied phosphodiesterases (PDEs) that specifically targets cGMP typically generated by nitric oxide (NO)-mediated activation of the soluble guanylyl cyclase. Nitric Oxide 139-151 phosphodiesterase 5A Homo sapiens 21-25 32526061-6 2021 OBJECTIVES: Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. Nitric Oxide 84-96 phosphodiesterase 5A Homo sapiens 139-143 29687019-2 2018 Because phosphodiesterase-5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. Nitric Oxide 71-83 phosphodiesterase 5A Homo sapiens 8-27 31409013-13 2019 The increased nitric oxide sensitivity was not the result of a decreased PDE5 activity, as PDE5 activity was even increased. Nitric Oxide 14-26 phosphodiesterase 5A Homo sapiens 91-95 31339910-2 2019 This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. Nitric Oxide 93-105 phosphodiesterase 5A Homo sapiens 19-43 31339910-2 2019 This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. Nitric Oxide 93-105 phosphodiesterase 5A Homo sapiens 45-49 32744956-6 2021 The pro-apoptotic effect of Sildenafil through nitric oxide (NO)/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most common mechanisms. Nitric Oxide 47-59 phosphodiesterase 5A Homo sapiens 66-90 32744956-6 2021 The pro-apoptotic effect of Sildenafil through nitric oxide (NO)/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most common mechanisms. Nitric Oxide 47-59 phosphodiesterase 5A Homo sapiens 92-96 32202086-7 2021 Recent clinical and pre-clinical studies using human tissues suggested that new peripherally acting agents including the Max-K channel activator, guanylate cyclase activator, and nitric oxide donor could be potential therapies either as a monotherapy or in combination with PDE5-Is in ED patients. Nitric Oxide 179-191 phosphodiesterase 5A Homo sapiens 274-278 33115566-4 2020 Topadur Pharma has invented small molecular weight nitric oxide-releasing PDE5 inhibitors, which by modulating a key enzyme system of intracellular signaling may address chronic non-healing wounds. Nitric Oxide 51-63 phosphodiesterase 5A Homo sapiens 74-78 32872119-4 2020 Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Nitric Oxide 44-56 phosphodiesterase 5A Homo sapiens 151-170 31110491-4 2019 In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Nitric Oxide 41-53 phosphodiesterase 5A Homo sapiens 9-13 30701875-2 2018 Until recently, the only therapeutic strategy to influence the molecular pathway of nitric oxide (NO) - soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) was the use of phosphodiesterase type 5 inhibitors (PDE-5 inhibitors), such as sildenafil. Nitric Oxide 84-96 phosphodiesterase 5A Homo sapiens 228-233 29687019-2 2018 Because phosphodiesterase-5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. Nitric Oxide 71-83 phosphodiesterase 5A Homo sapiens 29-33 28379598-2 2017 It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. Nitric Oxide 105-117 phosphodiesterase 5A Homo sapiens 18-42 28964803-3 2017 We thus hypothesized that in cells expressing the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate - PDE5 (NO-sGC-cGMP-PDE5) pathway such as platelets, the presence of NO increases the intracellular cGMP content and thus promotes the intracellular accumulation of sildenafil or tadalafil. Nitric Oxide 50-62 phosphodiesterase 5A Homo sapiens 125-129 28964803-3 2017 We thus hypothesized that in cells expressing the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate - PDE5 (NO-sGC-cGMP-PDE5) pathway such as platelets, the presence of NO increases the intracellular cGMP content and thus promotes the intracellular accumulation of sildenafil or tadalafil. Nitric Oxide 50-62 phosphodiesterase 5A Homo sapiens 131-147 27419107-6 2016 Moreover, the studies to evaluate the influence of nitric oxide (NO) and guanosine monophosphate (cGMP) signaling pathway associated with PDE5 showed both cancer reduction and cancer development. Nitric Oxide 51-63 phosphodiesterase 5A Homo sapiens 138-142 27903966-0 2017 PDE5 inhibitors enhance the lethality of pemetrexed through inhibition of multiple chaperone proteins and via the actions of cyclic GMP and nitric oxide. Nitric Oxide 140-152 phosphodiesterase 5A Homo sapiens 0-4 27903966-1 2017 Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. Nitric Oxide 144-156 phosphodiesterase 5A Homo sapiens 0-19 27903966-1 2017 Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. Nitric Oxide 144-156 phosphodiesterase 5A Homo sapiens 21-25 26620458-2 2016 The constant discoveries of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cell-signaling pathway for smooth muscle (SM) control in other urogenital tracts (UGTs) make PDE5-Is promising pharmacologic agents against other benign urological diseases. Nitric Oxide 28-40 phosphodiesterase 5A Homo sapiens 177-181 26530829-8 2016 A phosphodiesterase type 5 (PDE5) inhibitor (1 muM tadalafil) disrupted the spontaneous Ca(2+) transient synchrony and abolished vasomotion in a nitric oxide (NO)-dependent manner. Nitric Oxide 145-157 phosphodiesterase 5A Homo sapiens 28-60 26093192-3 2015 In the present study, we found that PDE5 activity and expression were regulated by S-nitrosylation, a covalent modification of cysteine residues by nitric oxide (NO). Nitric Oxide 148-160 phosphodiesterase 5A Homo sapiens 36-40 27872007-1 2016 INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Nitric Oxide 143-155 phosphodiesterase 5A Homo sapiens 14-33 27872007-1 2016 INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Nitric Oxide 143-155 phosphodiesterase 5A Homo sapiens 35-39 26205960-5 2015 PDE5 was the major cGMP phosphodiesterase responsible for reducing nitric oxide- and natriuretic peptide-induced cGMP signals. Nitric Oxide 67-79 phosphodiesterase 5A Homo sapiens 0-4 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Nitric Oxide 85-97 phosphodiesterase 5A Homo sapiens 256-281 26047999-3 2015 The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. Nitric Oxide 100-112 phosphodiesterase 5A Homo sapiens 29-34 26027619-1 2015 BACKGROUND: Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. Nitric Oxide 21-33 phosphodiesterase 5A Homo sapiens 273-277 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Nitric Oxide 85-97 phosphodiesterase 5A Homo sapiens 283-288 25799991-3 2015 Furthermore, although PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signalling is often depressed by heart disease. Nitric Oxide 38-50 phosphodiesterase 5A Homo sapiens 22-27 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Nitric Oxide 183-195 phosphodiesterase 5A Homo sapiens 0-19 24341639-2 2014 Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Nitric Oxide 89-101 phosphodiesterase 5A Homo sapiens 21-26 25051133-2 2014 PDE5 inhibitors can induce vasodilation; in addition, through a complex pathway involving nitric oxide, cyclic guanosine monophosphate, and protein kinase G, it can reduce apoptosis and suppress cell proliferation. Nitric Oxide 90-102 phosphodiesterase 5A Homo sapiens 0-4 24157969-4 2013 The decrease in relaxation in response to the nitric oxide (NO) donor was accompanied by a decrease in cGMP levels and an increase in phosphodiesterase 5 (PDE5) activity. Nitric Oxide 46-58 phosphodiesterase 5A Homo sapiens 134-153 24157969-4 2013 The decrease in relaxation in response to the nitric oxide (NO) donor was accompanied by a decrease in cGMP levels and an increase in phosphodiesterase 5 (PDE5) activity. Nitric Oxide 46-58 phosphodiesterase 5A Homo sapiens 155-159 26138471-4 2015 This brief review will focus on two therapies that are already approved for use in the US for other indications: PDE-5 inhibition to preserve nitric oxide - cGMP signaling to promote vasodilation and inhibition of the endothelin type A receptor to reduce vascular contraction. Nitric Oxide 142-154 phosphodiesterase 5A Homo sapiens 113-118 24877179-11 2014 CONCLUSIONS: Nebivolol potentiated the capacity of PDE5 inhibitors to relax vascular structures of erectile tissue from diabetic patients by enhancing the nitric oxide (NO)/cGMP pathway in these tissues. Nitric Oxide 155-167 phosphodiesterase 5A Homo sapiens 51-55 24432631-1 2013 The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Nitric Oxide 210-222 phosphodiesterase 5A Homo sapiens 11-30 24432631-1 2013 The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Nitric Oxide 210-222 phosphodiesterase 5A Homo sapiens 32-37 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Nitric Oxide 183-195 phosphodiesterase 5A Homo sapiens 21-26 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Nitric Oxide 183-195 phosphodiesterase 5A Homo sapiens 78-83 23475211-0 2013 Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate. Nitric Oxide 73-85 phosphodiesterase 5A Homo sapiens 0-24 23475211-0 2013 Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate. Nitric Oxide 73-85 phosphodiesterase 5A Homo sapiens 26-30 23421435-4 2013 : To assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5-i nonresponders compared with healthy controls. Nitric Oxide 27-39 phosphodiesterase 5A Homo sapiens 148-152 23382484-2 2013 Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Nitric Oxide 51-63 phosphodiesterase 5A Homo sapiens 0-24 23382484-2 2013 Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Nitric Oxide 51-63 phosphodiesterase 5A Homo sapiens 26-30 22948216-10 2012 Thus, enhancement of the nitric oxide/cyclic guanosine monophosphate signaling pathway by vardenafil attenuates and reverts fibroblast-to-myofibroblast trans-differentiation, hypothesizing that BPH patients might benefit from long-term therapy with PDE5 inhibitors. Nitric Oxide 25-37 phosphodiesterase 5A Homo sapiens 249-253 23018163-7 2013 In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. Nitric Oxide 124-136 phosphodiesterase 5A Homo sapiens 34-38 23086989-0 2012 Melatonin inhibits nitric oxide signaling by increasing PDE5 phosphorylation in coronary arteries. Nitric Oxide 19-31 phosphodiesterase 5A Homo sapiens 56-60 22948216-6 2012 Enhancement of nitric oxide/cyclic guanosine monophosphate signaling by vardenafil, sodium nitroprusside, or PDE5 knockdown reduced smooth muscle cell actin and IGF binding protein 3 mRNA and protein levels and restored fibroblast-like morphology in trans-differentiated myofibroblast. Nitric Oxide 15-27 phosphodiesterase 5A Homo sapiens 109-113 22067410-3 2012 We hypothesized that modulation of pulmonary vascular hypertone by oversignalling of the nitric oxide pathway with phosphodiesterase 5 (PDE5) inhibition might be beneficial. Nitric Oxide 89-101 phosphodiesterase 5A Homo sapiens 115-134 22248110-9 2012 The PDE5 may exert their influence by increasing the levels of nitric oxide both centrally (reducing sympathetic drive) and peripherally (leading to smooth-muscle dilatation of the seminal tract). Nitric Oxide 63-75 phosphodiesterase 5A Homo sapiens 4-8 21950284-1 2012 Vardenafil hydrochloride (HCl) is a potent and selective phosphodiesterase type-5 (PDE-5) inhibitor that enhances nitric oxide (NO)-mediated relaxation of human corpus cavernosum and NO-induced rabbit penile erection, and enhances erectile function in patients. Nitric Oxide 114-126 phosphodiesterase 5A Homo sapiens 57-81 21950284-1 2012 Vardenafil hydrochloride (HCl) is a potent and selective phosphodiesterase type-5 (PDE-5) inhibitor that enhances nitric oxide (NO)-mediated relaxation of human corpus cavernosum and NO-induced rabbit penile erection, and enhances erectile function in patients. Nitric Oxide 114-126 phosphodiesterase 5A Homo sapiens 83-88 22028410-6 2012 The PDE5i zaprinast significantly increased prostate strip relaxation to the nitric oxide donor sodium nitroprusside (SNP) in control but not castrated rats. Nitric Oxide 77-89 phosphodiesterase 5A Homo sapiens 4-8 22067410-3 2012 We hypothesized that modulation of pulmonary vascular hypertone by oversignalling of the nitric oxide pathway with phosphodiesterase 5 (PDE5) inhibition might be beneficial. Nitric Oxide 89-101 phosphodiesterase 5A Homo sapiens 136-140 21269399-2 2011 The efficacy of PDE5 inhibitors is limited because a minimum amount of nitric oxide (NO) is necessary. Nitric Oxide 71-83 phosphodiesterase 5A Homo sapiens 16-20 21697861-4 2011 It has been suggested that human clitoral corpus cavernosum smooth muscle is regulated by nitric oxide (NO)/cyclic GMP and related key enzymes, such as NO synthases (NOSs) and the phosphodiesterase type 5 (PDE5). Nitric Oxide 90-102 phosphodiesterase 5A Homo sapiens 180-204 21697861-4 2011 It has been suggested that human clitoral corpus cavernosum smooth muscle is regulated by nitric oxide (NO)/cyclic GMP and related key enzymes, such as NO synthases (NOSs) and the phosphodiesterase type 5 (PDE5). Nitric Oxide 90-102 phosphodiesterase 5A Homo sapiens 206-210 21762988-7 2011 RESULTS: By selectively inhibiting PDE-5, tadalafil causes nitric oxide-mediated vasodilation in the pulmonary vasculature. Nitric Oxide 59-71 phosphodiesterase 5A Homo sapiens 35-40 21702653-2 2011 The antipulmonary hypertensive effects of nitric oxide and the natriuretic peptides are mediated via increasing intracellular cGMP and enzymatic degradation by PDE-5 is the major route of cGMP inactivation in the lung. Nitric Oxide 42-54 phosphodiesterase 5A Homo sapiens 160-165 20347789-2 2010 Newer clinical strategies to preferentially lower pulmonary pressures and pulmonary vascular tone improve functional performance and symptoms of heart failure by targeting the nitric oxide signal transduction pathways, as with PDE5 inhibition. Nitric Oxide 176-188 phosphodiesterase 5A Homo sapiens 227-231 20668100-0 2010 Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat. Nitric Oxide 92-104 phosphodiesterase 5A Homo sapiens 16-35 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Nitric Oxide 130-142 phosphodiesterase 5A Homo sapiens 4-23 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Nitric Oxide 130-142 phosphodiesterase 5A Homo sapiens 25-30 19945540-1 2010 Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. Nitric Oxide 237-249 phosphodiesterase 5A Homo sapiens 114-119 21036891-2 2011 PDE5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. Nitric Oxide 44-56 phosphodiesterase 5A Homo sapiens 0-4 20698857-10 2010 Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals. Nitric Oxide 160-172 phosphodiesterase 5A Homo sapiens 19-23 20698857-10 2010 Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals. Nitric Oxide 160-172 phosphodiesterase 5A Homo sapiens 64-68 20698857-10 2010 Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals. Nitric Oxide 160-172 phosphodiesterase 5A Homo sapiens 64-68 20480269-3 2010 Treatment with phosphodiesterase type 5 (PDE5) inhibitors aimed at decreasing breakdown of nitric oxide (NO) is a mainstay of treatment for ED. Nitric Oxide 91-103 phosphodiesterase 5A Homo sapiens 15-39 20480269-3 2010 Treatment with phosphodiesterase type 5 (PDE5) inhibitors aimed at decreasing breakdown of nitric oxide (NO) is a mainstay of treatment for ED. Nitric Oxide 91-103 phosphodiesterase 5A Homo sapiens 41-45