Central leptin sensitization of angiotensin II‐induced hypertension (858.3)

Abstract

Obesity has been associated with selective leptin resistance whereby the anorexic effect of leptin is attenuated, but its action to increase sympathetic nervous activity (SNA) and blood pressure (BP) remains intact. A recent study showed an interaction between leptin and the renin angiotensin system in regulating SNA. Our previous studies using an Induction‐Delay‐Expression experimental design have demonstrated that a subpressor dose of angiotensin (ANG) II pretreatment sensitizes the brain to produce an enhanced hypertensive response to a subsequent treatment with pressor dose of ANG II. The present study tested the hypothesis that central chronic leptin pretreatment can also sensitize the pressor actions of ANG II. Male rats were implanted for telemetered BP recording and were pretreated during Induction with either peripheral subpressor ANG II (10 ng/kg/min) or central leptin (20 ng/kg/min) for one week. After one week Delay, rats were treated during Expression with subcutaneous ANG II (120 ng/kg/min) for 2 weeks. The animals with the subpressor ANG II pretreatment responded with enhanced hypertension to ANG II (Δ44.5±3.4 mmHg vs.Δ 21.2±5.2 mmHg). Central infusion of leptin during Induction mimicked the sensitization produced by the subpressor ANG II (Δ39.3±3.8 mmHg). The results indicate that central chronic leptin can predispose rats to display an enhanced ANG II‐elicited hypertensive response.