Isoproterenol impairs the rat coronary vasculature: effects of angiotensin-converting enzyme inhibition.
The purpose of the present study was to evaluate whether in addition to its myocardial effects, chronic beta-adrenergic stimulation with isoproterenol could modify the coronary vasculature. For this purpose, rats were treated for 2 weeks with isoproterenol, and the hearts were isolated for determination of the minimal coronary vascular resistance under maximal vasodilation and then perfused-fixed for morphometry of the coronary arteries. In addition, because isoproterenol stimulates the renin-angiotensin system (RAS), the effects of angiotensin-converting enzyme (ACE) inhibition on the coronary vasculature were assessed. Isoproterenol increased heart weight by 65% and minimal coronary resistance by 55%. This effect was associated with medial thickening in intermediate (32%) and large coronary arterioles (26%). Cilazapril, a long-acting ACE inhibitor, completely prevented the medial thickening induced by isoproterenol and normalized the minimal coronary resistance. We conclude that impairment of the rat coronary vasculature induced by chronic beta-adrenergic stimulation might be in part mediated by activation of the RAS.
Roux
S
S
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Clozel
J P
JP
Fischli
W
W
Kuhn
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D012083:Renin; D007545:Isoproterenol