Most studies on myocardial hypertrophy during hypertension are based on young animals, a limitation which precludes an adequate understanding of the heart's response to the more common adult onset of hypertension. Our previous work suggests that age and the duration of hypertension play important roles in modulating left ventricular hypertrophy and its associated changes. Accordingly, the proposed research will test the hypothesis that when the onset and progression of hypertension occur during middle or late life the left ventricle develops structural and functional abnormalities which are exacerbated by prolonged periods of hypertension. We will study two age groups of rats with renovascular (Goldblatt, two kidney, one clip) hypertension of either 3 or 6 mos. duration. To test the hypothesis that some left ventricular abnormalities may not be reversible when hypertension develops late in life we will also study animals following the reversal of hypertension with antihypertensive therapy. Left ventricular performance will be assessed by measuring indices of cardiac output during acutely increased preload. To delineate specific alterations in subcellular components of the myocardial cell which may underlie functional changes, electron and light microscopy and morphometry will be employed, and the subepi- and subendo-cardial regions of the left ventricle compared. Because it is recognized that the coronary vasculature and circulation may be adversely affected by hypertension and/or myocardial hypertrophy, regional and total myocardial perfusion will be measured at rest and during maximal vasodilation, and coronary reserve estimated. As a corollary to the perfusion studies the extensiveness of the capillary bed and the structure of the coronary arteries will be evaluated by microscopy and image analysis. To determine whether any of the alterations characteristic of hypertension and its reversal are model dependent, we will also employ rats with mineralcorticoid hypertension in some of the experiments. These studies will provide new and basic insights regarding the impact of age and the duration of hypertension on the heart.
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