Endothelial dysfunction of hindquarter resistance vessels in experimental heart failure.
Local vascular alterations may contribute to increased peripheral vasoconstriction in chronic heart failure. To test whether endothelial dysfunction might be involved, the effect of acetylcholine, nitroglycerin, and NG-monomethyl-L-arginine (L-NMMA) was investigated in a constant-flow perfused hindquarter of rats with and without chronic heart failure (CHF) due to myocardial infarction. Changes in perfusion pressure were measured as an index of changes in hindlimb vascular resistance. The endothelium-dependent vasodilator effect of acetylcholine was significantly reduced in rats with large infarcts (greater than 40% of the left ventricle). However, the endothelium-independent vasodilator effect of nitroglycerin and the vasoconstrictor effect of L-NMMA were similar for infarct and normal animals. The vasodilator response to acetylcholine was partially inhibited by pretreatment with L-NMMA. Thus the basal release of nitric oxide from hindquarter resistance vessels is preserved in CHF. However, the endothelium-mediated dilation in response to acetylcholine is attenuated, in part, due to a depressed stimulated release of nitric oxide. The latter mechanism might be involved in the impaired vasodilatory capacity in the peripheral circulation in CHF, e.g., during exercise.
Drexler
H
H
Medizinische Klinik III, University of Freiburg, Federal Republic of Germany.
Lu
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000503:physiopathology; D002303:Cardiac Output, Low / Q000209:etiology / Q000503:physiopathology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine