HEMODYNAMIC AND RENAL RESPONSES TO CHRONIC HYPERINSULINEMIA IN OBESE,INSULIN-RESISTANT DOGS

We previously reported that chronic hyperinsulinemia does not cause hy pertension in normal insulin-sensitive dogs. However, resistance to th e metabolic and vasodilator effects of insulin may be a prerequisite f or hyperinsulinemia to elevate blood pressure. The present study teste d this hypothesis by comparing the control of systemic hemodynamics an d renal function during chronic hyperinsulinemia in instrumented norma l conscious dogs (n=6) and in dogs made obese and insulin resistant by feeding them a high-fat diet for 6 weeks (n=6). After 6 weeks of the high-fat diet, body weight increased from 24.0+/-1.2 to 40.9+/-1.2 kg, arterial pressure rose from 83+/-5 to 106+/-4 mm Hg, and cardiac outp ut rose from 2.98+/-0.29 to 5.27+/-0.54 L/min. Insulin sensitivity, as sessed by fasting hyper insulinemia and by the hyperinsulinemic euglyc emic clamp technique, was markedly reduced in obese dogs. Insulin infu sion (1.0 mU/kg per minute for 7 days) in obese dogs elevated plasma i nsulin from 42+/-12 mu U/mL to 95 to 219 mu U/mL but failed to increas e arterial pressure, which averaged 106+/-4 mm Hg during control and 1 02+/-4 mm Hg during 7 days of insulin infusion. Hyperinsulinemia for 7 days in obese dogs elevated heart rate from 116+/-8 to 135+/-7 beats per minute but caused no significant changes in cardiac output, in con trast to normal dogs (n=6), in which marked increases in cardiac outpu t (31+/-5% after 7 days) and decreases in total peripheral resistance occurred during chronic insulin infusion. Thus, chronic hyperinsulinem ia did not raise blood pressure in obese dogs even though they were re sistant to the metabolic and vasodilator effects of insulin. These obs ervations provide no evidence that hyperinsulinemia causes hypertensio n, even in the presence of insulin resistance, in obese dogs.