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 end-diastolic 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 in 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.(ABSTRACT TRUNCATED AT 250 WORDS)