Differential modulation of leptin-induced sympathoexcitation by baroreflex activation

Abstract

Objective: Leptin induces increases in sympathetic nerve activity to various regions. This has implications for energy balance, thermogenesis and possibly cardiovascular regulation. The aim of the present study was to test the hypothesis that the increases in sympathetic nerve activity induced by leptin in different regions respond differentially to baroreflex activation.

Methods: A total of 24 anesthetized male Sprague-Dawley rats were assigned to either leptin (0.5 mg/kg body weight bolus i.v., followed by 0.5 mg/kg body weight i.v. during 3 h, n = 12) or vehicle (n = 12) treatment. Mean arterial pressure (MAP), heart rate (HR), interscapular brown adipose tissue sympathetic nerve activity (IBAT-SNA) and renal sympathetic nerve activity (RSNA) were recorded continuously. Before and 3 h after start of leptin or vehicle, baroreceptor activity was decreased by lowering MAP with nitroprusside and increased by raising MAP with phenylephrine.

Results: Compared with vehicle, leptin significantly increased IBAT-SNA (294 +/- 78%) and RSNA (211 +/- 28%), while not altering MAP (117 +/- 5 versus 118 +/- 4 mmHg). Baroreflex activation by phenylephrine completely suppressed the leptin-induced increase in RSNA. In contrast, the leptin-induced increase in IBAT-SNA could not be overridden by baroreflex activation. Compared with vehicle, leptin did not significantly alter the maximum gain of the RSNA-MAP (-3.8 +/- 0.7 versus -2.7 +/- 0.3% of maximum mmHg-1, NS) or the IBAT-SNA-MAP curves (-1.9 +/- 0.7 versus -1.4 +/- 0.3% of maximum mmHg-1, NS).

Conclusions: Leptin-induced regional increases in sympathetic nerve activity respond non-uniformally to baroreflex activation. The increase in RSNA can be suppressed by baroreflex activation, suggesting that the leptin-induced increase in RSNA subserves circulatory functions. In contrast, the increase in IBAT-SNA with leptin is not prevented by baroreflex activation, suggesting the recruitment of sympathetic fibers that serve thermogenic or metabolic and not circulatory functions.