LATE ONSET RENAL-HYPERTENSION IN OLD RATS ALTERS LEFT-VENTRICULAR STRUCTURE AND FUNCTION

This study was designed to test the hypothesis that the left ventricle of the senescent rat has a limited compensatory response to late onset hypertension. Data were obtained from middle-aged (15 mo) and senescent (24 mo) Sprague-Dawley rats either 1 or 3 mo after the initiation of one-kidney, figure-8 renal wrap (Grollman) hypertension. Peak left ventricular (LV) function assessed during acute volume expansion was not markedly affected 1 mo after induction of hypertension with the exception of a decrement in the acceleration of aortic flow (dF/dt) in the senescent hypertensive group. Three months after the surgery was performed, peak LV function (stroke index, stroke volume/g LV, and dF/dt) was depressed in the senescent hypertensive rats, compared with the controls. In contrast, these indexes in the 15-mo-old rats were similar in the experimental and control groups after either 1 or 3 mo of hypertension. Developed pressure, however, was not compromised by hypertension at either age. Cardiocyte hypertrophy due to pressure overload occurred in both age groups but to a greater extent in the senescent group. This cellular response did not cause an absolute increase in LV mass and was associated with endomyocardial foci of cellular degeneration and fibrosis suggestive of cell loss. Mitochondria-to-myofibril volume ratios were not significantly altered in the experimental groups at either age, thus the cellular hypertrophy in these rats was characterized by uniform organelle growth. These data support two important conclusions regarding late onset hypertension. First, although the capacity for cardiocyte hypertrophy is not lost in middle age and senescence, our findings suggest that a substantial cell loss occurs, particularly in the senescent rat. Second, peak LV function is compromised in senescent but not middle-aged rats.