Long term evolution of peripheral resistance artery structure and endothelial function in a rat model of chronic heart failure. effect of angiotensin converting enzyme inhibition. Mulder, Paul, Lahcen Elfertak, Vincent Richard, Patricia Compagnon, Bruno Devaux, Jean-Paul Henry, Elizabeth Scalbert, Pierre Desch[acute]e, Bertrand Mac[acute]e, Christian Thuillez. Departments of Pharmacology, VACOMED, IFRMP n degrees 23 and Histology, Rouen University Medical School, Rouen, France
APStracts 3:0026H, 1996.
Chronic heart failure (CHF) is characterized by systemic vasoconstriction and is accompanied by an impaired endothelium -dependent relaxation of large arteries. We investigated in a rat model of CHF 1) whether such endothelial dysfunction also exists in peripheral resistance arteries, 2) whether this is associated with vascular morphological changes, and 3) whether angiotensin-converting enzyme (ACE) inhibition affects small artery structure and endothelial function. Rats with CHF, induced by coronary artery ligation, were chronically treated with placebo or the ACE inhibitor perindopril (2mg/kg/day), starting 7 days post ligation. Endothelium -dependent vasodilation to acetylcholine was assessed before treatment, then after 1 month or 1 year of treatment in isolated and perfused femoral and mesenteric artery segments. The presence of CHF was confirmed by reduced left ventricular (LV) systolic pressure and LV dP/dt, and increased LVEDP and central venous pressure. CHF reduced the vasodilatory response to acetylcholine, and this was more marked in femoral than in mesenteric arteries, whereas the response to the nitric oxide donor nitroprusside was unaffected. However, CHF did not induce any remodeling of the two arteries studied. Perindopril prevented cardiac hypertrophy and decreased blood pressure, central venous pressure and LVEDP without affecting LV dP/dt. In small arteries, perindopril improved the response to acetylcholine and reduced media cross sectional area and collagen density. At the level of small peripheral arteries, CHF induces an endothelial dysfunction, but does not affect vascular structure. ACE inhibition prevents the CHF-induced endothelial dysfunction and induces both cardiac and vascular remodeling. The vascular changes could contribute to the beneficial effects of ACE inhibitors on hemodynamics and survival in chronic heart failure. 

Received 30 October 1995; accepted in final form 8 January 1996.
APS Manuscript Number H1009-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96