EFFECTS OF ENALAPRIL AND AMLODIPINE ON SMALL-ARTERY STRUCTURE AND COMPOSITION, AND ON ENDOTHELIAL DYSFUNCTION IN SPONTANEOUSLY HYPERTENSIVERATS

Objectives To determine whether an angiotensin converting enzyme inhib itor, enalapril, and a dihydropyridine calcium channel antagonist, aml odipine, regress the altered structure, media composition, and vascula r relaxation of small arteries of spontaneously hypertensive rats. Met hods Spontaneously hypertensive rats aged 10 weeks were treated for 12 weeks with 10 mg/kg per day enalapril or 10-20 mg/kg per day amlodipi ne and compared with age-matched untreated spontaneously hypertensive rats. Small coronary, renal, mesenteric, and femoral arteries (lumen d iameter 200-250 mu m) were studied isometrically on a wire myograph, a nd mesenteric arteries isobarically as pressurized vessels. The compos ition of the vascular media of the latter was studied by electron micr oscopy. Results Blood pressure, and cardiac and aortic hypertrophy wer e reduced in treated spontaneously hypertensive rats. Treatment signif icantly decreased media thickness and media:lumen ratio of coronary, r enal, mesenteric, and femoral small arteries studied isometrically and of pressurized mesenteric small arteries. Media cross-sectional area was smaller for coronary arteries studied isometrically and mesenteric arteries studied isobarically. Electron microscopic analysis revealed an increase in collagen:elastin ratio in the media of spontaneously h ypertensive rat vessels, and a decrease under treatment to levels foun d in Wistar-Kyoto rats, with no significant changes detected in smooth muscle cells. The amplitude of contractions induced by acetylcholine on wire-myograph-mounted mesenteric arteries from spontaneously hypert ensive rats were decreased by treatment and relaxation of pressurized arteries induced by acetylcholine was normalized. Conclusion Treatment of spontaneously hypertensive rats with enalapril or with amlodipine resulted in regression of cardiovascular hypertrophy and amelioration of endothelial dysfunction. Morphometric results obtained using an iso metric myograph and a pressurized preparation to study rat small arter ies were closely correlated. Regression of structural remodeling in sm all arteries was outward hypotrophic, with a reduction in the collagen :elastin ratio, and without net change in the absolute and relative v olumes of smooth muscle and number of smooth muscle layers. (C) 1998 L ippincott-Raven Publishers.