Hemodynamic and Renal Responses to Chronic Hyperinsulinemia in Obese, Insulin-Resistant Dogs

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Abstract
We previously reported that chronic hyperinsulinemia does not cause hypertension in normal insulin-sensitive dogs. However, resistance to the metabolic and vasodilator effects of insulin may be a prerequisite for hyperinsulinemia to elevate blood pressure. The present study tested this hypothesis by comparing the control of systemic hemodynamics and renal function during chronic hyperinsulinemia in instrumented normal 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 output rose from 2.98±0.29 to 5.27±0.54 L/min. Insulin sensitivity, assessed by fasting hyperinsulinemia and by the hyperinsulinemic euglycemic clamp technique, was markedly reduced in obese dogs. Insulin infusion (1.0 mU/kg per minute for 7 days) in obese dogs elevated plasma insulin from 42±12 μU/mL to 95 to 219 μU/mL but failed to increase arterial pressure, which averaged 106±4 mm Hg during control and 102±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 contrast to normal dogs (n=6), in which marked increases in cardiac output (31±5% after 7 days) and decreases in total peripheral resistance occurred during chronic insulin infusion. Thus, chronic hyperinsulinemia did not raise blood pressure in obese dogs even though they were resistant to the metabolic and vasodilator effects of insulin. These observations provide no evidence that hyperinsulinemia causes hypertension, even in the presence of insulin resistance, in obese dogs.