Abstract
We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors
-
Adult
-
Cyclic GMP / metabolism
-
Drug Synergism
-
Female
-
Humans
-
In Vitro Techniques
-
Male
-
Middle Aged
-
Nitric Oxide Donors / pharmacology*
-
Nitroprusside / pharmacology*
-
Phosphodiesterase Inhibitors / pharmacology
-
Piperazines / pharmacology*
-
Pulmonary Artery / drug effects*
-
Pulmonary Artery / physiology
-
Purines
-
Sildenafil Citrate
-
Sulfones
-
Vasodilation / drug effects
-
Vasodilator Agents / pharmacology*
Substances
-
Nitric Oxide Donors
-
Phosphodiesterase Inhibitors
-
Piperazines
-
Purines
-
Sulfones
-
Vasodilator Agents
-
Nitroprusside
-
Sildenafil Citrate
-
3',5'-Cyclic-GMP Phosphodiesterases
-
Cyclic GMP