SUMMARY To study the early effects of hypertension on the heart, we examined isolated hearts from rabbits with slowly developing hypertension of up to 64 weeks in duration after unilateral nephrectomy and renal artery stenosis. Normotensive animals kept under identical conditions served as controls. Mean arterial blood pressure rose from 83 to 155 mm Hg in the hypertensive group of longest duration, but the ratio of left ventricular weight to body weight was not different between the experimental and control groups. Although left ventricular hypertrophy was not present, left ventricular peak systolic pressure of perfused hearts was significantly higher in hypertensive than in normotensive hearts. Furthermore, while in hypertensive hearts the left ventricular end-diastolic volume was increased, the peak systolic pressure did not respond to an increase in left ventricular enddiastolic volume. Functional changes were accompanied by metabolic changes in the left ventricle. Rates of glucose utilization were increased and rates of ketone body utilization were decreased hi hypertensive hearts. Activities of key enzymes of carbohydrate metabolism (phosphorylase, hexokinase, phosphofructokinase, and lactate dehydrogenase) were increased, while those of ketone body metabolism (3-oxoacid-CoA transferase, acetoacetyl-CoA synthase) were decreased and those of the citric acid cycle (citrate synthase, 2-oxoglutarate dehydrogenase) were not different between groups. In summary, moderate hypertension for a period of more than 1 year resulted in functional and metabolic changes of the left ventricle in hypertensive animals that were already manifest at 8 weeks of hypertension. The mechanism for the structural and functional adaptations that characterize the response of the left ventricle to hypertension may rest in changes of enzyme activities and resultant changes in substrate supply of the heart. (Hypertension 11: 416-426, 1988) KEY WORDS • renovascular hypertension activities * left ventricular function H YPERTENSION increases cardiac work by increasing plasma volume and peripheral vascular resistance. Sustained hypertension leads to changes in cardiac function and energy metabolism and, ultimately, to the development of cardiac hypertrophy. Adaptation of the heart to a high cardiac work load is important for survival of the organism as a whole and is governed by derepression of genetic information, leading to new synthesis of contractile proteins, mitochondria, and enzyme systems of myocardial energy production. Received February 17, 1987; accepted December 23, 1987. cardiac substrate metabolism • cardiac enzyme Acute pressure overload of the heart in experiments using banding of either the pulmonary artery or the aorta leads to rapid development of hypertrophy and a decrease in contractility in isolated papillary muscles, as measured by the rate of force development and the velocity of shortening by extrapolation to zero stress. 1More recent studies have reported decreased tensiondependent heat production and actin-act...

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