CORONARY VASCULAR FUNCTION AFTER HEMORRHAGIC HYPOTENSION IN DOGS

This study tested the hypothesis that hemorrhagic hypotension alters i ntrinsic contraction-relaxation mechanisms of coronary arteries. Coron ary vascular smooth muscle (VSM) was evaluated ex vivo using left circ umflex coronary artery preparations isolated from beagle dogs 4 hr aft er sham hemorrhage (controls) or maintained hemorrhagic hypovolemia. H emorrhaged dogs exhibited systemic hypotension (mean arterial pressure almost-equal-to 65 mm Hg), tachycardia, and tachypnea during the 4 hr in vivo phase of the study, accompanied by 30-50% reductions in left ventricular myocardial blood flows (P < 0.05). Coronary arteries isola ted from these dogs were stretched to the asymptote of their length-co ntractile tension relationship; no significant differences were observ ed in length-active tension or length-passive tension relations betwee n hemorrhage and control arteries. Similarly, neither the maximal resp onses nor the EC50 values for isometric contractions produced by prost aglandin F2alpha (PGF2alpha) (10(-8) to 3 x 10(-5) M) or depolarizing concentrations of K+ (10-100 mM) were altered by hemorrhage (P > 0.05) . Vasodilator responses to the cyclic guanosine monophosphate (GMP)-de pendent VSM relaxant nitroprusside (10(-4) M) also were not prevented by the hemorrhage protocol. In contrast, coronary VSM relaxation induc ed by the endothelium-dependent vasodilator acetylcholine (10(-9)-10(- 5) M) was significantly decreased by 25-50% in K+- and PGF2alpha-preco ntracted coronary arteries from the hemorrhaged dogs (P < 0.01). We co nclude that receptor (PGF2alpha)-dependent and membrane depolarization (K+)-dependent contractile mechanisms remained operational in coronar y arteries during hemorrhagic hypotension, as did basal cyclic GMP-dep endent VSM relaxation mechanisms. However, diminution of acetylcholine -induced relaxation of coronary VSM suggests impaired endothelium-depe ndent vasodilation in the coronary vasculature during acute (4 hr) hem orrhagic hypotension. (C) 1993 Wiley-Liss, Inc.