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  • Title: Effects of enalapril and amlodipine on small-artery structure and composition, and on endothelial dysfunction in spontaneously hypertensive rats.
    Author: Sharifi AM, Li JS, Endemann D, Schiffrin EL.
    Journal: J Hypertens; 1998 Apr; 16(4):457-66. PubMed ID: 9797191.
    Abstract:
    OBJECTIVES: To determine whether an angiotensin converting enzyme inhibitor, enalapril, and a dihydropyridine calcium channel antagonist, amlodipine, regress the altered structure, media composition, and vascular relaxation of small arteries of spontaneously hypertensive rats. METHODS: 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 amlodipine and compared with age-matched untreated spontaneously hypertensive rats. Small coronary, renal, mesenteric, and femoral arteries (lumen diameter 200-250 microm) were studied isometrically on a wire myograph, and mesenteric arteries isobarically as pressurized vessels. The composition of the vascular media of the latter was studied by electron microscopy. RESULTS: Blood pressure, and cardiac and aortic hypertrophy were reduced in treated spontaneously hypertensive rats. Treatment significantly decreased media thickness and media: lumen ratio of coronary, renal, 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 hypertensive rat vessels, and a decrease under treatment to levels found 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 hypertensive 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 isometric myograph and a pressurized preparation to study rat small arteries were closely correlated. Regression of structural remodeling in small arteries was outward hypotrophic, with a reduction in the collagen: elastin ratio, and without net change in the absolute and relative volumes of smooth muscle and number of smooth muscle layers.
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