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Renin as a risk factor for atherogenesis

Part 3. Effects of hypercholesterolemia, hyporeninemia and one-kidney-one-clip hypertension in the rabbit
  • Merrill L. Overturf
    Correspondence
    Reprint requests to: Merrill L. Overturf, Ph.D., The University of Texas Medical School, Internal Medicine/Hypertension, Room 1278 MSMB, P.O. Box 20708, Houston, TX 77025, U.S.A.
    Affiliations
    Department of Medicine, The University of Texas Medical School, and the Department of Pathology, Baylor College of Medicine, Houston, TX U.S.A.
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  • Harley D. Sybers
    Affiliations
    Department of Medicine, The University of Texas Medical School, and the Department of Pathology, Baylor College of Medicine, Houston, TX U.S.A.
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  • Robert E. Druilhet
    Affiliations
    Department of Medicine, The University of Texas Medical School, and the Department of Pathology, Baylor College of Medicine, Houston, TX U.S.A.
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  • Walter M. Kirkendall
    Affiliations
    Department of Medicine, The University of Texas Medical School, and the Department of Pathology, Baylor College of Medicine, Houston, TX U.S.A.
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      Abstract

      The purpose of this study was to test the hypothesis that plasma renin activity (PRA) is a risk factor for cardiovascular disease. Four groups of New Zealand rabbits were used to study the effects of PRA and hypertension on atherogenesis. Control groups were fed normal rabbit chow (Group I), or normal chow supplemented with 0.25% cholesterol (Group III) Group II animals were fed normal chow, had a clip placed around the left renal artery and were contralaterally nephrectomized (one-kidney-one-clip, 1K-1C). The renal arteries and kidneys of Group IV animals, which were fed a cholesterol diet, were manipulated similarly. Blood pressure and blood chemistry measurements were performed periodically over a 7-month period. The blood pressure was unaffected by either diet; however, PRA and aldosterone levels were greatly reduced in the 1 K-1 C groups (Groups II and IV). No atheroma were observed in any of the animals consuming the normal diet (Groups I and II) despite sharply elevated blood pressure in the Group II animals. Medial hypertrophy of small muscular arteries was observed in several Group II animals. All of the animals fed the atherogenic diet showed extensive aortic atheromata. There was, however, a significantly smaller lesion index for the normotensive cholesterol-fed animals (Group III) than those with increased blood pressure (Group IV). Likewise, microscopic evaluation of the aorta, coronary arteries, renal arteries, and kidneys mirrored this difference in the vascular involvement between the animals of Groups III and IV. We conclude that neither relatively high nor low PRA levels affect the development of atherosclerosis or other cardiovascular lesions. However, hypertension with a concomitantly high cholesterol diet acts synergistically in exacerbating atherogenesis.

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