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(Hypertension. 2009;53:375.)
© 2009 American Heart Association, Inc.

Original Articles Part 2

Leptin Signaling in the Nucleus Tractus Solitarii Increases Sympathetic Nerve Activity to the Kidney

Allyn L. Mark; Khristofor Agassandian; Donald A. Morgan; Xuebo Liu; Martin D. Cassell; Kamal Rahmouni

From the Departments of Internal Medicine (A.L.M., D.A.M., X.L., K.R.) and Anatomy and Cell Biology (K.A., M.D.C.) and Center on Functional Genomics of Hypertension (A.L.M., K.A., D.A.M., X.L., M.D.C., K.R.), Carver College of Medicine, University of Iowa, Iowa City.

Correspondence to Allyn L. Mark, 3187 MERF, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1101. E-mail allyn-mark{at}uiowa.edu

The hypothalamic arcuate nucleus was initially regarded as the principal site of leptin action, but there is increasing evidence for functional leptin receptors in extrahypothalamic sites, including the nucleus tractus solitarii (NTS). We demonstrated previously that arcuate injection of leptin increases sympathetic nerve activity (SNA) to brown adipose tissue and kidney. In this study, we tested the hypothesis that leptin signaling in the NTS affects sympathetic neural outflow. Using a stereotaxic device in anesthetized rats, we microinjected leptin (0.25 to 1.00 µg) or saline into the NTS while recording SNA to kidney and brown adipose tissue. Microinjection of leptin into the commissural and medial subnuclei of the caudal NTS at the level of the area postrema in Sprague-Dawley rats produced a dose-related increase in renal SNA (+112±15% with leptin 1 µg; n=7; P<0.001) but did not increase SNA to brown adipose tissue (–15±12%; P value not significant). This effect depended on intact functional leptin receptors, because it was not observed in Zucker obese rats that have a missense mutation in the leptin receptor. Rostral NTS injection of leptin failed to increase SNA, indicating that leptin signaling in the NTS is probably confined to the caudal NTS at the level of the area postrema. In summary, this study demonstrates that leptin signaling in the caudal NTS increases SNA to the kidney but not to the brown adipose tissue. The study strengthens the concept of a distributed brain network of leptin action and demonstrates that these distributed brain sites can mediate contrasting sympathetic responses to leptin.

Key Words: leptin • nucleus tractus solitarii • sympathetic nerve activity • kidney • brown adipose tissue

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