Renovascular beta adrenergic hypersensitivity and hyperinsulinemia in rats with dietary-induced obesity

To determine whether obesity alters responsiveness to vasoactive drugs, we compared the cardiovascular effects of angiotensin, phenylephrine and isoproterenol in unanesthetized age-matched control and obese Oscai rats. Obesity was induced by programming pups to overeat immediately after birth and then feeding them a high-fat diet thereafter. Elevations in tail-cuff systolic and mean pressures from 7 through 11 months of age and in plasma insulin at 8 months of age indicated that obese rats had developed borderline hypertension and hyperinsulinemia. Cardiovascular responsiveness was then tested by recording blood pressure, heart rate and renal blood flow from chronically implanted arterial catheters and flow probes while graded doses of the three test drugs were infused intravenously. Heart rate and renal blood flow decreased during pressor responses to angiotensin and phenylephrine and were oppositely increased during depressor responses to isoproterenol. Magnitude of all cardiovascular receptors was dose-dependent. Obese rats had weaker reflex bradycardic responses to angiotensin and phenylephrine than control rats. More importantly, they also had larger renal vasoconstrictor responses to 2 ng/100 g of angiotensin or vasodilator responses to 15 ng/100 of isoproterenol. Whether or not the changes in cardiovascular responsiveness were related to hyperinsulinemia was undetermined. Our results suggest that, in addition to being overweight, slightly hypertensive and hyperinsulinemic, obese Oscai rats have impaired baroreflexes and a renal vascular bed more responsive to beta adrenergic vasodilation.