Faculty Collaboration Database

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity. Am J Physiol Heart Circ Physiol 2012 Jul 15;303(2):H197-206

Date

05/23/2012

Pubmed ID

22610169

Pubmed Central ID

PMC3404702

DOI

10.1152/ajpheart.00974.2011

Scopus ID

2-s2.0-84864011880 (requires institutional sign-in at Scopus site)   98 Citations

Abstract

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT(1a)R(-/-)), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT(1a)R(-/-) vs. AT(1a)R(+/+) mice. ICV leptin in rats increased AT(1a)R and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT(1a)R mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake.

Author List

Hilzendeger AM, Morgan DA, Brooks L, Dellsperger D, Liu X, Grobe JL, Rahmouni K, Sigmund CD, Mark AL

Authors

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adipose Tissue
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors
Animals
Body Weight
Brain
Captopril
Corticotropin-Releasing Hormone
Eating
Gene Deletion
Leptin
Losartan
Male
Mice
Mice, Inbred C57BL
Peptidyl-Dipeptidase A
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Renin-Angiotensin System
Sympathetic Nervous System
alpha-MSH