Pulmonary vascular smooth muscle relaxation by cAMP-mediated pathways.
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) beta2-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 beta2-adrenergic receptor activation was most effective as complete ring relaxation was achieved at 10(-6) M isoproterenol with a median effective dose of 10(-7) M. A2, P2, and EP2-receptor activation all achieved complete ring relaxation at concentrations up to 10(-3) M. Relaxation by H2-receptor activation was least effective as 30% ring tension remained at a concentration of 10(-3) M. We conclude that these receptor-linked pathways, although all mediated through cAMP, have significant differences in potency and efficacy.
Fullerton
D A
DA
Department of Surgery, University of Colorado, Denver 80262, USA.
Agrafojo
J
J
McIntyre
R C
RC
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D018343:Receptors, Adrenergic, beta-2; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D000527:Alprostadil; D000241:Adenosine; D007545:Isoproterenol; D017259:Dimaprit