Impaired endothelium-dependent relaxation in large, but not small arteries in rats after coronary ligation.
Vascular responses were studied in both large and small arteries of rats following 8 weeks of heart failure produced by coronary ligation. Responses to noradrenaline, acetylcholine and sodium nitroprusside were studied in isolated thoracic aorta and mesenteric arteries. In the aorta, concentration-response curves for noradrenaline were similar between heart failure and sham animals and unaffected by the nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG). Relaxation by acetylcholine was impaired in heart failure rats (EC50-6.79 log M heart failure vs. -7.15 log M sham). In the presence of L-NOARG, relaxation by acetylcholine was completely abolished in rings from sham rats, whereas constriction was observed in rings from heart failure rats. Relaxation by sodium nitroprusside was not different between sham and heart failure rats. In mesenteric arteries, responses to noradrenaline, acetylcholine and sodium nitroprusside were not different between heart failure and sham rats. L-NOARG reduced the maximum response to acetylcholine in both heart failure (82% to 50%) and shams (89% to 49%) by a similar magnitude, with no effect on relaxation to sodium nitroprusside. These data suggest that acetylcholine-induced relaxation is impaired in the aorta, but not mesenteric arteries in rats with heart failure. The mechanism is not solely due to impaired nitric oxide release and may be due to acetylcholine-induced contraction.
Prior
D L
DL
Alfred and Baker Medical Unit, Baker Medical Research Institute, Prahran, Victoria, Australia.
Jennings
G L
GL
Arnold
P
P
Du
X J
XJ
Chin-Dusting
J P
JP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D003327:Coronary Disease / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine