Coronary vascular function after hemorrhagic hypotension in dogs.
This study tested the hypothesis that hemorrhagic hypotension alters intrinsic contraction-relaxation mechanisms of coronary arteries. Coronary vascular smooth muscle (VSM) was evaluated ex vivo using left circumflex coronary artery preparations isolated from beagle dogs 4 hr after sham hemorrhage (controls) or maintained hemorrhagic hypovolemia. Hemorrhaged dogs exhibited systemic hypotension (mean arterial pressure approximately 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 isolated from these dogs were stretched to the asymptote of their length-contractile tension relationship; no significant differences were observed in length-active tension or length-passive tension relations between hemorrhage and control arteries. Similarly, neither the maximal responses nor the EC50 values for isometric contractions produced by prostaglandin F2 alpha (PGF2 alpha) (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)-dependent VSM relaxant nitroprusside (10(-4) M) also were not prevented by the hemorrhage protocol. In contrast, coronary VSM relaxation induced by the endothelium-dependent vasodilator acetylcholine (10(-9)-10(-5) M) was significantly decreased by 25-50% in K(+)- and PGF2 alpha-precontracted coronary arteries from the hemorrhaged dogs (P < 0.01). We conclude that receptor (PGF2 alpha)-dependent and membrane depolarization (K+)-dependent contractile mechanisms remained operational in coronary arteries during hemorrhagic hypotension, as did basal cyclic GMP-dependent VSM relaxation mechanisms. However, diminution of acetylcholine-induced relaxation of coronary VSM suggests impaired endothelium-dependent vasodilation in the coronary vasculature during acute (4 hr) hemorrhagic hypotension.
Parker
J L
JL
John M. Dalton Research Center, University of Missouri, Columbia 65211.
Shelton
J A
JA
Defily
D V
DV
Gute
D
D
Laughlin
M H
MH
Adams
H R
HR
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D015237:Dinoprost / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D006470:Hemorrhage / Q000503:physiopathology*; D007022:Hypotension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012039:Regional Blood Flow; D012771:Shock, Hemorrhagic / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D009569:Nitric Oxide; D015237:Dinoprost; D000109:Acetylcholine; D011188:Potassium