Endotoxin impairs flow-induced vasodilation of porcine coronary arterioles.
The purpose of this study was to test the hypothesis that endotoxemia impairs endothelium-dependent (both receptor-mediated and flow-induced) vasodilation in porcine coronary arterioles. Coronary arterioles were isolated from three groups of 4- to 8-wk old (10.3 +/- 0.8 kg) pigs: endotoxemic (E; 250 micrograms/kg endotoxin iv), control (C; equal volume of saline), and untreated pigs (UT). Subepicardial arterioles (60-120 microns) were isolated and cannulated with two micropipettes that were connected to two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O throughout the experiments. All C vessels developed spontaneous tone and exhibited flow-induced vasodilation from 65 to 95% maximal diameter. Spontaneous tone developed in only three of five arterioles from E pigs, and flow-induced vasodilation was not observed in any arteriole from E pigs. Spontaneous tone developed in all six arterioles isolated from UT pigs but disappeared in four of these vessels as a result of 1 h of in vitro incubation with endotoxin (2.5 micrograms/ml). Flow-induced vasodilation was also abolished in these vessels after 1 h of endotoxin exposure. Incubation with 3 mM L-arginine, in vitro, restored flow-induced vasodilation in E arterioles and endotoxin-treated UT arterioles. Vasoconstriction induced by acetylcholine (ACh) and vasodilation induced by nitroprusside (NP) and bradykinin (BK) were similar in arterioles from all groups. In contrast, endotoxin impairs flow-induced vasodilation of coronary arterioles. The mechanism responsible for the impairment of flow-induced vasodilation seems to reside in disruption of the L-arginine/nitric oxide pathway.
Kuo
L
L
Department of Medical Physiology, Texas A&M University, College Station 77843.
Chilian
W M
WM
Davis
M J
MJ
Laughlin
M H
MH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D004731:Endotoxins; D000109:Acetylcholine; D001920:Bradykinin