Central Receptors Mediating the Cardiovascular Actions of Melanocyte Stimulating Hormones.
From: Division of Nephrology, San Francisco General Hospital and University of California San Francisco, San Francisco, California 94143-1341, USA.
Journal of hypertension
- Publish Date: Nov 2006
- ISSN: 0263-6352
- Volume: 24
- Issue: 11
- Pages: 2239-46
- Medium: Print
- Language: English
- Citation (JAMA): Ni Xi-Ping, Butler Andrew A, Cone Roger D, et al. Central Receptors Mediating the Cardiovascular Actions of Melanocyte Stimulating Hormones.. J. Hypertens. Nov 2006;24:2239-46
Abstract
OBJECTIVE: Alpha and gamma-melanocyte stimulating hormones (MSH) are peptides that possess potent hypertensinogenic actions when injected intravenously or intracerebroventricularly. We sought to define the central receptor(s) mediating these cardiovascular actions. METHODS: We gave bolus injections of synthetic alpha or gamma-MSH intravenously or intracerebroventricularly to anesthetized wild-type (Mc3r+/+, Mc4r+/+) mice and mice with targeted disruption of the gamma-MSH receptor (Mc3r-/-) or the melanocortin 4 receptor (Mc4r-/-). RESULTS: Gamma-MSH injected intravenously increased mean arterial pressure (MAP) and heart rate (HR) dose-dependently, with the effect being evident at 10 mol/kg; the maximum increase, at 10 mol/kg, was 38 mmHg in both strains from similar control MAP. Parallel increases in HR also occurred. Injection of the sodium channel blocker, benzamil, 4 microg/kg intracerebroventricularly, before intravenous gamma-MSH completely prevented the increases in MAP and HR in both strains. Injection of 2 x 10 mol/g body weight alpha-MSH intravenously had no effect on MAP or HR in Mc4r wild-type or -/- mice. However, the same dose given intracerebroventricularly to wild-type mice increased MAP from 76 +/- 4 to 95 +/- 5 mmHg at 10 min (P < 0.01) and HR from 416 +/- 15 to 480 +/- 15 beats/min (P < 0.01). In Mc4r-/- mice, the intracerebroventricular administration of the peptide did not alter these variables, in contrast to the results in wild-type mice. CONCLUSION: Both MSH peptides exert their hypertensinogenic effects through central sites of action, which probably reflect the activation of sympathetic outflow. The actions of intracerebroventricular alpha-MSH appear to be mediated via Mc4r, whereas those of gamma-MSH are independent of its receptor Mc3r, but reflect the activation of a sodium channel in the central nervous system. These results help to reconcile the hypertensive action of gamma-MSH injections with the hypertension observed in states of gamma-MSH deficiency.
Mesh Headings (Keywords): Amiloride, Animals, Blood Pressure, Dose-Response Relationship, Drug, Heart Rate, Hypertension, Mice, Mice, Knockout, Models, Animal, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Sodium Channel Blockers, Sympatholytics, alpha-MSH, gamma-MSH
Check for Full Text / PubMed Unique Identifier (PMID): 17053546
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.