Interaction of Sildenafil With cAMP-Mediated Vasodilation In Vivo

ABSTRACT—Sildenafil inhibits cGMP breakdown by phosphodiesterase 5. In vitro, increased cGMP levels inhibit cAMP breakdown by phosphodiesterase 3. It is uncertain, however, whether sildenafil increases biological effects of interventions increasing cAMP levels in vivo. The objective of the present s...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2002-11, Vol.40 (5), p.763-767
Main Authors: Schalcher, Christoph, Schad, Karin, Brunner-La Rocca, Hans Peter, Schindler, Ruth, Oechslin, Erwin, Scharf, Christoph, Suetsch, Gabor, Bertel, Osmund, Kiowski, Wolfgang
Format: Article
Language:English
Subjects:
Adrenergic beta-Agonists - pharmacology
Adult
Blood Pressure - drug effects
Brachial Artery - drug effects
Brachial Artery - physiology
Cyclic AMP - metabolism
Cyclic GMP - metabolism
Forearm - blood supply
Heart Rate - drug effects
Hemodynamics - drug effects
Humans
Isoproterenol - pharmacology
Male
Milrinone - pharmacology
Nitroglycerin - pharmacology
Phosphodiesterase Inhibitors - pharmacology
Piperazines - pharmacology
Purines
Regional Blood Flow - drug effects
Sildenafil Citrate
Sulfones
Vasodilation - drug effects
Vasodilation - physiology
Vasodilator Agents - pharmacology
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Summary:ABSTRACT—Sildenafil inhibits cGMP breakdown by phosphodiesterase 5. In vitro, increased cGMP levels inhibit cAMP breakdown by phosphodiesterase 3. It is uncertain, however, whether sildenafil increases biological effects of interventions increasing cAMP levels in vivo. The objective of the present study in 40 healthy male volunteers was to determine the existence and extent of interactions with sildenafil and vasodilators acting via cGMP or cAMP or independently from these mediators on the arterial tone of the human forearm. Forearm blood flow (FBF) responses (plethysmography) to brachial artery infusions of 3 doses each of nitroglycerin, which increases cGMP levels; of isoprenaline and milrinone, which increase cAMP levels; and of verapamil as a control were assessed at baseline and 80 minutes after 50 mg oral sildenafil in 10 volunteers each. Sildenafil increased FBF (2.5±0.1 to 3.5±0.2 mL/min per 100 mL, P
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.0000036027.71527.3E