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.

Abstract

The effects of trandolapril, a converting enzyme inhibitor (CEI), on left ventricular (LV) diastolic stiffness and coronary vascular resistance (CVR), were studied with an isolated heart preparation in 15-month-old spontaneously hypertensive rats (SHR). The hypertensive animals were 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 (BP). 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 chamber or tissue stiffness. Five-minute anoxia resulted in the same dramatic increase in chamber stiffness in every experimental group. During anoxia, as during normoxia, tissue stiffness was still greater in SHR than in WKY. A major effect of CEI was to normalize the tissue stiffness of SHR under anoxia. Coronary vascular resistance (CVR) was increased in SHR as compared with WKY. Trandolapril improves CVR and significantly shifts the coronary pressure flow curve to the dilatory side. Both collagen concentration (approximately 2 mg/g) and the content in slow V3 myosin isoform, used as biologic markers of cardiac senescence, were the same in the three experimental groups, but higher than in young hearts. Trandolapril had no effect on these parameters. In semisenescent SHR, despite having rather slight effect on arterial pressure, trandolapril 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 parallel with reduction in LV hypertrophy (LVH).