REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY BY CONVERTING-ENZYME INHIBITION IN 12-15-MONTH-OLD SPONTANEOUSLY HYPERTENSIVE RATS - EFFECTS ON CORONARY RESISTANCE AND VENTRICULAR COMPLIANCE IN NORMOXIA AND ANOXIA

The effects of trandolapril, a converting enzyme inhibitor (CEI), on l eft ventricular (LV) diastolic stiffness and coronary vascular resista nce (CVR), were studied with an isolated heart preparation in 15-month -old spontaneously hypertensive rats (SHR). The hypertensive animals w ere treated for 3 months with trandolapril (0.3 mg/kg/day) (SHRT), and compared with untreated age-matched Wistar-Kyoto rats (WKY) and SHR. Trandolapril treatment resulted in 15% diminution in blood pressure (B P). In contrast, it completely normalized left ventricular (LV) weight . Untreated SHR, as compared with WKY, had a dilated LV and increased diastolic tissue stiffness. Trandolapril had no effect on either chamb er or tissue stiffness. Five-minute anoxia resulted in the same dramat ic increase in chamber stiffness in every experimental group. During a noxia, as during normoxia, tissue stiffness was still greater in SHR t han in WKY. A major effect of CEI was to normalize the tissue stiffnes s of SHR under anoxia. Coronary vascular resistance (CVR) was increase d in SHR as compared with WKY. Trandolapril improves CVR and significa ntly shifts the coronary pressure flow curve to the dilatory side. Bot h collagen concentration (similar to 2 mg/g) and the content in slow V 3 myosin isoform, used as biologic markers of cardiac senescence, were the same in the three experimental groups, but higher than in young h earts. Trandolapril had no effect on these parameters. In semisenescen t SHR, despite having rather slight effect on arterial pressure, trand olapril completely normalized LV weight. In addition, collagen content and its physiologic counterpart, tissue stiffness, were unaffected by 3-month treatment with trandolapril. Nevertheless, the anoxia-induced increase in LV tissue stiffness was improved by trandolapril in paral lel with reduction in LV hypertrophy (LVH).