This Article Free upon publication Full Text Full Text (PDF) Data Supplement All Versions of this Article: 54/5/1001    most recent HYPERTENSIONAHA.109.138065v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Arnold, A. C. Articles by Diz, D. I. PubMed PubMed Citation Articles by Arnold, A. C. Articles by Diz, D. I. Pubmed/NCBI databases Substance via MeSH Related Collections Obesity Animal models of human disease Hypertension - basic studies Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2009;54:1001.)
© 2009 American Heart Association, Inc.

Original Articles

Leptin Impairs Cardiovagal Baroreflex Function at the Level of the Solitary Tract Nucleus

From the Hypertension and Vascular Research Center and Physiology and Pharmacology Department, Wake Forest University School of Medicine, Winston-Salem, N.C.

Correspondence to Debra I. Diz, Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1032. E-mail ddiz{at}wfubmc.edu

Circulating leptin is elevated in some forms of obesity-related hypertension, associated with impaired baroreflex function. Leptin receptors are present on vagal afferent fibers and neurons within the solitary tract nucleus, providing an anatomic distribution consistent with baroreflex modulation. Although solitary tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant effect on baroreflex sensitivity for control of the heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired baroreflex sensitivity for bradycardia in response to increases in pressure (1.15±0.04 versus 0.52±0.12 ms/mm Hg; P<0.01). Transgenic ASrAOGEN rats with low brain angiotensinogen have an upregulation of the leptin receptor and p85 mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with these observations, the response to leptin was enhanced in ASrAOGEN rats, because both the 144-fmol (1.46±0.08 versus 0.75±0.10 ms/mm Hg; P<0.001) and 500-fmol (1.36±0.32 versus 0.44±0.06 ms/mm Hg; P<0.05) leptin microinjections impaired baroreflex sensitivity. At these doses, leptin microinjection had no effect on resting pressure, heart rate, or the tachycardic response to decreases in pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites within the solitary tract nucleus impairs the baroreflex sensitivity for bradycardia induced by increases in arterial pressure, consistent with a permissive role in mediating increases in arterial pressure. Baroreflex inhibition was enhanced in animals with evidence of increased leptin receptor and relevant signaling pathway mRNA.

Key Words: leptin • solitary tract nucleus • transgenic rats • angiotensin • baroreflex