The effect of obesity and weight reduction upon circulating concentrations of atrial natriuretic peptide was assessed in an experimental model of the disease. Obese rats weighing in excess of 750 g were compared with formerly obese animals subjected to a 15-week period of caloric restriction resulting in a 40% reduction in body weight. Mean adipocyte size was significantly reduced with weight loss, as was estimated body fat. Mean arterial blood pressure remained normotensive for both groups, but a significant reduction in heart rate was associated with weight reduction. Circulating atrial natriuretic peptide was significantly elevated in the lean rats, which also exhibited decreased plasma renin activity and a negative sodium balance. Analysis of heart to body weight ratios implied that an obesity-associated, volume-induced cardiac hypertrophy remained even after the normalization of body fat. These results suggest that the diuresis and natriuresis accompanying weight reduction may be facilitated by atrial natriuretic peptide, which was elevated in part due to a persistent left ventricular hypertrophy following the transition from the obese to lean condition.

To determine the biochemical and hemodynamic responses to aortic ligation, and to assess the survival rate after the induction of hypertension, 90 normotensive rats were subjected to surgical constriction of the abdominal aorta. Mortality, left ventricular hemodynamics, myocardial biochemical assays, and plasma renin assays were determined 1 week, 1 month, 3 months, or 1 year later. Mortality was greatest between 1 week and 3 months after aortic ligation, during which plasma renin activity was significantly elevated. The rate of left ventricular pressure rise, contractile index, and myocardial alpha-adrenoceptor number were increased at 1 month, but were comparatively depressed at 3 months after the operation, suggesting that the heart was in failure at this time. At 1 year after ligation, hemodynamic and biochemical parameters continued toward normalization. Our data suggest that, in this rodent model, cardiac pump failure occurs through a combination of time-dependent, pressure-induced mechanical adaptations and myocardial biochemical changes that involve both the renin-angiotensin and sympathetic nervous systems. The observed relationship between mortality, myocardial hemodynamics, and biochemical parameters may be used for additional basic research investigations concerning the early periods of cardiac failure.

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