Pulmonary Vascular Smooth Muscle Relaxation by cAMP-Mediated Pathways

• Published in: The Journal of surgical research 1996-03, Vol.61 (2), p.444-448
• Main Authors: Fullerton, David A., Agrafojo, Jeanette, McIntyre, Jr, Robert C.
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine Diphosphate - pharmacology; Alprostadil - pharmacology; Animals; Biological and medical sciences; Blood vessels and receptors; Cyclic AMP - physiology; Dimaprit - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Isoproterenol - pharmacology; Male; Muscle, Smooth, Vascular - physiology; Pulmonary Artery - physiology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-2 - physiology; Vasodilation - drug effects; Vertebrates: cardiovascular system
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1996.0143

Adenosine 3′,5′-cyclic monophosphate (cAMP)-mediated pulmonary vascular smooth relaxation is a principle mechanism of pulmonary vasomotor control. The purpose of this study was to compare the potency and efficacy of the following receptor-linked pathways of pulmonary vasorelaxation which are mediated by cAMP: (1) β2-adrenergic receptor activation (response to isoproterenol) (2) Adenosine A2-receptor activation (response to adenosine) (3) Prostaglandin EP2-receptor activation (response to prostaglandin E1) (4) Histamine H2-receptor activation (response to the H2-receptor agonist dimaprit) and (5) Purinergic P2-receptor activation (response to ADP). Cumulative concentration-response curves were generated in isolated rat pulmonary artery rings suspended on individual tensiometers. Five rats/ten pulmonary artery rings were studied for each agonist. Relaxation by β2-adrenergic receptor activation was most effective as complete ring relaxation was achieved at 10−6Misoproterenol with a median effective dose of 10−7M. A2, P2, and EP2-receptor activation all achieved complete ring relaxation at concentrations up to 10−3M.Relaxation by H2-receptor activation was least effective as 30% ring tension remained at a concentration of 10−3M.We conclude that these receptor-linked pathways, although all mediated through cAMP, have significant differences in potency and efficacy.