Pulmonary vascular smooth muscle relaxation by cGMP- versus cAMP-mediated mechanisms.
The purpose of this study was to examine and compare pulmonary vascular smooth muscle relaxation by clinically used agents as related to cGMP mediation (sodium nitroprusside, nitroglycerin) and cAMP mediation (isoproterenol, prostaglandin E1 (PGE1), and amrinone) in isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings were suspended on a fine wire tensiometer in individual organ chambers. After confirming the endothelial integrity of the rings (response to acetylcholine), the rings were preconstricted with phenylephrine 10(-6) M. Dose-response curves for sodium nitroprusside, nitroglycerin, isoproterenol, amrinone, and PGE1 were then generated. Each of these agents was tested on six rings. Each ring was tested with each agent in a random order. The doses of sodium nitroprusside, isoproterenol, and nitroglycerin required to produce relaxation of isolated pulmonary arterial rings were not statistically different, but were significantly less than those required by amrinone and PGE1 (P < 0.05). These data suggest that relaxation of pulmonary vascular smooth muscle is more readily achieved via cGMP by guanylate cyclase activation (sodium nitroprusside, nitroglycerin) and via beta-adrenergic cAMP mediation (isoproterenol) than via cAMP-mediated pathways requiring either prostaglandin receptor activation (PGE1) or phosphodiesterase inhibition (amrinone).
Fullerton
D A
DA
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Hahn
A R
AR
Banerjee
A
A
Harken
A H
AH
D000527:Alprostadil / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D011943:Receptors, Adrenergic, beta; D018078:Receptors, Prostaglandin E; D014665:Vasodilator Agents; D009599:Nitroprusside; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D000527:Alprostadil; D005996:Nitroglycerin; D006152:Cyclic GMP; D000676:Amrinone; D007545:Isoproterenol