Journal article
A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity
American journal of physiology. Heart and circulatory physiology, Vol.303(2), pp.H197-H206
07/15/2012
DOI: 10.1152/ajpheart.00974.2011
PMCID: PMC3404702
PMID: 22610169
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.
Details
- Title: Subtitle
- A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity
- Creators
- Aline M Hilzendeger - Center on Functional Genomics of Hypertension, Carver College of Medicine, University of Iowa, Iowa City, IowaDonald A Morgan - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa; andLeonard Brooks - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa; andDavid Dellsperger - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa; andXuebo Liu - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IowaJustin L Grobe - Center on Functional Genomics of Hypertension, Carver College of Medicine, University of Iowa, Iowa City, IowaKamal Rahmouni - Center on Functional Genomics of Hypertension, Carver College of Medicine, University of Iowa, Iowa City, IowaCurt D Sigmund - Center on Functional Genomics of Hypertension, Carver College of Medicine, University of Iowa, Iowa City, IowaAllyn L Mark - Center on Functional Genomics of Hypertension, Carver College of Medicine, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.303(2), pp.H197-H206
- DOI
- 10.1152/ajpheart.00974.2011
- PMID
- 22610169
- PMCID
- PMC3404702
- NLM abbreviation
- Am J Physiol Heart Circ Physiol
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- PO1-HL-084207; HL-061446; HL-098276 / National Institutes of Health
- Language
- English
- Date published
- 07/15/2012
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Cardiothoracic Surgery; Internal Medicine
- Record Identifier
- 9984040016702771
Metrics
48 Record Views