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Am J Physiol Regul Integr Comp Physiol (January 9, 2003). doi:10.1152/ajpregu.00480.2002
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Submitted on August 12, 2002
Accepted on December 30, 2002

Chronic Cardiovascular and Renal Actions of Leptin during Hyperinsulinemia

Jay J Kuo1*, Oscar B Jones1, and John E Hall1

1 Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

* To whom correspondence should be addressed. E-mail: jkuo{at}physiology.umsmed.edu.

Hyperinsulinemia and hyperleptinemia occur concurrently in obese subjects, and both have been suggested to mediate increased blood pressure associated with excess weight gain. The goal of this study was to determine whether chronic hyperinsulinemia exacerbates the effects of insulin on arterial pressure and renal function. Group I and II rats were infused with insulin (1.5 mU/kg/min) for 21 days while maintaining euglycemia. After 7 days of insulin infusion, Group II rats received leptin (1.0 µg/kg/min) for 7 days, concomitant with insulin. Insulin plus glucose infusion reduced food intake to 55±7% of control, while leptin+insulin lowered food intake further to 22±4% of the initial control. Insulin initially raised MAP by 12±1 mmHg; then MAP declined to 5-8 mmHg above control during continued hyperinsulinemia. Leptin+insulin infusion increased MAP by 7±2 mmHg above the level observed in rats infused with insulin alone. Insulin raised HR by 17±5 bpm, whereas leptin+insulin increased HR by 34±5 bpm. Thus, leptin appears to increase the effects of insulin to suppress appetite and to raise arterial pressure and heart rate.




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