Influence of a single dose of 20 mg tadalafil, a phosphodiesterase 5 inhibitor, on ambulatory blood pressure in subjects with hypertension

Patterson, D.; McInnes, Gordon T.; Webster, J; Mitchell, Malcolm; MacDonald, Thomas M.

doi:10.1111/j.1365-2125.2006.02658.x

Cited by 15 publications

(14 citation statements)

References 37 publications

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“…Their safety and appropriate use was reviewed in the second Princeton Consensus Conference recommendations, 2 and more recent analyses of placebo-controlled and postmarketing surveillance data have demonstrated no new concerns regarding cardiovascular events. 108,109 In fact, a variety of studies have demonstrated a potential role for PDE5 inhibition in the management of hypertension [110][111][112][113] and endothelial dysfunction [114][115][116] in patients at risk for CVD. Effects on endothelial function are believed to underlie the beneficial effect of PDE5 inhibition in patients with pulmonary hypertension, for which sildenafil and tadalafil are licensed for use.…”

Section: Mayo Clinic Proceedingsmentioning

confidence: 99%

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

Nehra

Jackson

Miner

et al. 2012

Mayo Clinic Proceedings

417

341

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The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction. T he Princeton Consensus Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The first conference convened in June 1999 to develop recommendations for clinical management of sexual dysfunction in men and women with known cardiovascular disease (CVD). This conference also provided a multidisciplinary forum for evaluation of the potential cardiovascular risk posed by sexual activity in atrisk patients. The first Princeton Consensus Conference recommendations 1 included stratification of patients by level of cardiac risk associated with sexual activity based on existing CVD. Those at low risk could initiate or resume sexual activity and be treated for sexual dysfunction. For those at high risk, sexual activity was deferred until the cardiac condition was stabilized. The second Princeton Consensus Conference convened in June 2004 and expanded the recommendations of the first conference to emphasize risk factor evaluation and lifestyle management for all men with erectile dysfunction (ED). 2 The second conference recommendations also incorporated new information on the appropriate use of phosphodiesterase type 5 (PDE5) inhibitors in men with ED and concomitant CVD.The third Princeton Consensus Conference took place November 8 to 10, 2010, in Miami Beach, Florida. The group revisited and updated their 2005 recommendations regarding the cardiovascular risk associated with sexual activity in men with known CVD. 2 In addition, the third conference focused on the predictive value of vasculogenic ED in assigning cardiovascular risk in men of all ages, with the primary objective being development of an approach to cardiovascular risk assessment in younger men with ED and no known CVD. The role of testosterone in erectile function and cardiovascular health and the utility of testosterone replacement...

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Section: Mayo Clinic Proceedingsmentioning

confidence: 99%

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

Nehra

Jackson

Miner

et al. 2012

Mayo Clinic Proceedings

417

341

View full text Add to dashboard Cite

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“…Five different isozymes of PDE are found in vascular smooth muscle: PDE1, which hydrolyzes preferentially cGMP and is Ca 2+ /calmodulin‐dependent; PDE2, a cGMP‐stimulated phosphodiesterase; PDE3 that hydrolyzes cAMP and is inhibited by cGMP; PDE4, cAMP‐specific phosphodiesterase; and PDE5 that hydrolyzes cGMP and is insensitive to Ca 2+ ‐calmodulin [8,9]. Thus, PDE inhibitors have considerable therapeutic utility for arterial hypertension, pulmonary hypertension, and erectile dysfunction by causing relaxation of smooth muscle [10–13].…”

Section: Introductionmentioning

confidence: 99%

Vasodilatory activity and antihypertensive profile mediated by inhibition of phosphodiesterase type 1 induced by a novel sulfonamide compound

Pontes

Antunes

Sudo

et al. 2011

Fundamemntal Clinical Pharma

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LASSBio-985 is a sulfonamide compound designed as a simplified structure of a nonselective phosphodiesterase type 4 (PDE-4) inhibitor that promotes vasodilatory activity in vitro. PDE are enzymes responsible for the hydrolysis of cyclic adenosine 3',5'- monophosphate and cyclic guanosine 3',5'-monophosphate. Five different isozymes of PDE are found in vascular smooth muscle (PDE1-PDE5). Aortic rings, with or without endothelium, from male normotensive and spontaneously hypertensive rats (SHR) were prepared for isometric tension recording. Blood pressure was measured in Wistar Kyoto (WKY) rats and SHR during intravenous infusion of LASSBio-985 (10 mg/kg/min) during 15 min. LASSBio-985 induced a concentration-dependent vasodilation in aortic rings from normotensive and SHR, which was almost completely inhibited in endothelium-denuded vessels. Vasodilatory activity was also reduced in endothelium-intact aortic rings that had been pretreated with N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide synthase inhibitor and 1H-[1,2,4]oxadiazolod[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. LASSBio-985-induced vasodilation was also inhibited by sildenafil (100 μm) and SQ 22536, a PDE5 inhibitor and adenylate cyclase inhibitor, respectively. To evaluate the involvement of some endothelial receptors, atropine, diphenhydramine, HOE 140, naloxone, propranolol, indomethacin, and wortmannin were tested, but none inhibited the effects of LASSBio-985. The residual effect observed on endothelium-denuded aortic rings was abolished by nicardipine, a voltage-sensitive-Ca(2+)-channel blocker. Intravenous infusion of LASSBio-985 (10 mg/kg/min) significantly reduced systolic and diastolic pressures in both WKY and SHR. LASSBio-985 is a compound with vasodilatory activity, which could be consequent to PDE1 inhibition and voltage-sensitive-Ca(2+)-channel blockade.

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“…4 Acute BP reductions have also been observed after single-dose administration of sildenafil (50 mg) or tadalafil (20 mg) when measured with ABPM. 5,6 Of particular relevance to our study of PF-00489791 is a study of multiple-dose administration of sildenafil in untreated hypertensive patients. 7 In that study, 50 mg of sildenafil or placebo was administered 3 times daily for 16 days in 25 subjects, in a crossover design.…”

Section: Bp Lowering Effectsmentioning

confidence: 99%

Blood Pressure Lowering Effects of a New Long-Acting Inhibitor of Phosphodiesterase 5 in Patients With Mild to Moderate Hypertension

et al. 2009

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Abstract-Inhibition of phosphodiesterase 5 is an attractive candidate mechanism for blood pressure (BP) lowering. In this study, a novel long-acting phosphodiesterase 5 inhibitor, PF-00489791, was evaluated in 133 patients with mild to moderate hypertension, randomized into 1 of 4 groups: placebo, 4 mg, 10 mg, and 20 mg titrated after 14 days of dosing to 40 mg. Study medication was administered once daily for 28 days. Ambulatory BP monitoring was used. There was a statistically significant decrease (compared with placebo) in mean daytime systolic BP on day 28 at the 10 and 20/40 mg doses (by Ϸ5 and Ϸ7 mm Hg, respectively). Changes in mean daytime diastolic BP corresponded with those in systolic BP. The magnitude of BP lowering was greater on day 1 than on days 14 and 28, but the response was sustained between days 14 and 28. PF-00489791 also exerted BP lowering effects on mean 24-hour ambulatory BP. There was a dose-related increase in plasma cGMP concentration (statistically significant at the 20/40 mg dose). There was an increased incidence of headaches at the 10 and 20/40 mg doses (22% and 21%, respectively, compared with 12% with placebo) and an increased incidence of dyspepsia/gastroesophageal reflux disease and musculoskeletal adverse events at the 20/40 mg dose. In conclusion, PF-00489791 causes a clinically meaningful and sustained BP lowering in patients with hypertension. It is generally safe and well tolerated at the clinically efficacious doses. Key Words: hypertension Ⅲ phosphodiesterase 5 Ⅲ PDE-5 inhibition Ⅲ PF-00489791 Ⅲ ABPM Ⅲ cGMP Ⅲ blood pressure I nhibition of phosphodiesterase 5 (PDE-5) is an attractive candidate mechanism for blood pressure (BP) lowering. PDE-5 is an enzyme that, among several other tissues, is also expressed in human arterial and venous vascular smooth muscle (VSM) cells, 1,2 where it mediates the breakdown of cGMP by metabolizing it to inactive 5Ј-GMP. Elevated cGMP reduces levels of intracellular calcium and thereby produces relaxation of arterial VSM cells and hence a decrease in arterial vascular resistance. Thus, inhibition of PDE-5 should lead to an increase in intracellular cGMP, arterial and venous vasorelaxation, and a consequent reduction in systemic arterial BP. In the present study, we evaluated BP lowering effects of a novel long-acting PDE-5 inhibitor, PF-00489791, in patients with mild to moderate hypertension. Methods Study Subjects and Study DesignPatients were recruited and the study was conducted at 17 participating study centers in the United States. Written informed consent was obtained from each study participant. The final protocol and informed consent documentation were reviewed and approved by the institutional review board at each of the investigational centers. The study was registered on ClinicalTrials.gov.Study subjects included males and females of nonchildbearing potential, between the ages of 18 and 70 years, who had a history of mild to moderate hypertension that was currently controlled with antihypertensive medication, or, if untreated, ...

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Influence of a single dose of 20 mg tadalafil, a phosphodiesterase 5 inhibitor, on ambulatory blood pressure in subjects with hypertension

Cited by 15 publications

References 37 publications

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

Vasodilatory activity and antihypertensive profile mediated by inhibition of phosphodiesterase type 1 induced by a novel sulfonamide compound

Blood Pressure Lowering Effects of a New Long-Acting Inhibitor of Phosphodiesterase 5 in Patients With Mild to Moderate Hypertension

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