Impact of enalapril therapy on in vitro coronary artery responsiveness in pacing-induced heart failure.
In vitro coronary artery responsiveness to angiotensin I, angiotensin II, noradrenaline, phenylephrine, BHT 920, and potassium chloride together with functional relaxation to acetylcholine was investigated in dogs with pacing-induced heart failure treated with enalapril (oral administration of 10 mg.day-1) for a mean duration of 26 days. Although maximal responses generated to both angiotensin I and angiotensin II were unaltered in the enalapril-treated group, angiotensin II became more potent following enalapril treatment: the EC50 for angiotensin II following placebo treatment was 2.4 (0.6-5.8; 95% confidence limits) nM and following enalapril treatment was 0.03 (0.007-0.1; 95% confidence limits) nM. In addition to the above changes, coronary artery rings from dogs treated with enalapril developed significantly less tension to noradrenaline, phenylephrine, and BHT 920. In contrast, responses to potassium chloride were unaltered following enalapril treatment. However, the relaxation to acetylcholine was enhanced from 38.9 +/- 3.0 to 50.4 +/- 3.5% (placebo versus enalapril, p < 0.05). These findings indicate that enalapril may possess alpha-blocking properties and enhance the relaxation response to acetylcholine through an endothelial-dependent mechanism in addition to inhibiting converting enzyme.
Forster
C
C
Department of Medicine, University of Toronto, St. Michael's Hospital, Ont. Canada.
Larosa
G
G
Armstrong
P W
PW
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004656:Enalapril / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D066298:In Vitro Techniques; D008297:Male; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D000109:Acetylcholine