Chronic cardiovascular and renal actions of leptin: role of adrenergic activity.

Abstract

This study was designed to determine the role of changes in adrenergic activity in mediating the chronic cardiovascular, renal, and metabolic actions of leptin. Male Sprague-Dawley rats were implanted with catheters for mean arterial pressure (MAP) and heart rate (HR) measurements and IV infusions of either vehicle (n= 7) or alpha- and beta-adrenergic receptor antagonists, terazosin and propranolol (10 mg/kg/d; n= 8) throughout the study. After control measurements, murine leptin was infused IV (1.0 microg/kg/min) for 7 days along with vehicle or adrenergic antagonists, followed by a 7-day recovery period. Leptin infusion significantly reduced food intake in control rats from 22.6 +/- 0.8 to 10.6 +/- 0.4 g/d and, in adrenergic blockade rats, from 22.6 +/- 0.8 to 13.2 +/- 0.8 g/d. Fasting plasma insulin decreased from 48 +/- 10 to 5 +/- 2 microU/mL in control rats and from 51+/- 9 to 9 +/- 2 microU/mL in adrenergic blockade rats during leptin infusion. Leptin infusion did not significantly alter glomerular filtration rate in either group. MAP and HR increased by 6 +/- 1 mm Hg and 23 +/- 7 bpm after 7 days of leptin infusion in control rats. However, in adrenergic blockade rats, leptin infusion did not significantly alter MAP (-1 +/- 1 mm Hg) and decreased, rather than increased, HR (-23 +/- 8 bpm). These results indicate that leptin-induced increases in blood pressure and tachycardia are mediated by increased adrenergic activity and support the concept that leptin may be an important link between obesity, increased sympathetic activity, and hypertension. However, the chronic effects of leptin on insulin and glucose regulation do not appear to be altered by alpha- and beta-adrenergic receptor blockade.