Functional and biochemical analyses of isolated rat hearts in renal and reversed renal hypertension

Abstract

The present study evaluates cardiac function, plasma renin activity (PRA) and left ventricular (LV) myosin isoenzymes in untreated two-kidney, one-clip Goldblatt hypertensive rats (2KIC) and in 2KIC treated with felodipine and metoprolol. Normotensive rats (NCR) and another group of 2KIC, in which the renal artery constriction was removed (UC-2KIC), were also investigated. Cardiac performance was assessed by means of a working heart perfusion device, allowing also for measurements of myocardial oxygen consumption. Following antihypertensive therapy and unclipping, blood pressure became close to normotensive levels. PRA remained equally elevated in treated and untreated 2KIC, but became practically normalized after unclipping. Relative LV weight in 2KIC increased 74% above that in NCR but in treated 2KIC increased by only 20%. In UC-2KIC LV hypertrophy became reversed, LV weight/body being about the same as in treated 2KIC. In treated 2KIC, coronary resistance at maximal dilatation was significantly reduced, implying prevention of hypertensive, structural coronary vascular changes, and optimal LV function was improved markedly in the lower range of perfusion pressures compared with untreated 2KIC. When, however, the hearts were challenged at a high pumping resistance (perfusion pressure), LV function was similar in untreated and treated 2KIC. Myocardial oxygen consumption for given levels of stroke work was significantly lower in treated than in untreated 2KIC. The myosin isoenzyme pattern in the LV of 2KIC was shifted, with significantly higher amounts of VM-3 than in NCR. This shift was normalized by antihypertensive therapy or by unclipping. In conclusion, antihypertensive therapy with felodipine and metoprolol prevents the development of coronary vascular and left ventricular hypertrophy in 2KIC. This may contribute to enhance cardiac performance at low aortic pressure. The lack of improvement in optimal cardiac performance (at high aortic pressure) implies that the hypertensive state per se, rather than extent of pressure elevation, cardiac hypertrophy, or changes of LV isoenzymes, determines the reduced cardiac function in renal hypertensive rats (Friberg & Nordborg 1986).