This Article Full Text Full Text (PDF) All Versions of this Article: 41/3/768    most recent 01.HYP.0000048194.97428.1Av1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuo, J. J. Articles by Hall, J. E. Search for Related Content PubMed PubMed Citation Articles by Kuo, J. J. Articles by Hall, J. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB SODIUM Related Collections Obesity Animal models of human disease Other hypertension Energy metabolism Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2003;41:768.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Hypothalamic Melanocortin Receptors and Chronic Regulation of Arterial Pressure and Renal Function

From the Department of Physiology and Biophysics, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.

Correspondence to John E. Hall, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail jehall{at}physiology.umsmed.edu

This study examined control of cardiovascular and renal function during chronic melanocortin-3/4 receptor (MC3/4-R) activation or inhibition. Arterial and venous catheters were implanted in Sprague-Dawley rats for measurements of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and for intravenous infusions, and the lateral ventricle was cannulated for chronic intracerebroventricular (ICV) infusions. In experiment 1, after a 5-day control period, rats were administered the MC3/4-R agonist MTII (n=7, 10 ng/h ICV) or 0.9% saline (n=6, ICV) for 14 days, followed by a 5-day recovery period. In experiment 2, after a 5-day control period, rats were administered the MC3/4-R antagonist SHU-9119 (n=7, 1 nmol/h ICV) or 0.9% saline vehicle (n=7, ICV), or pair-fed during SHU-9119 infusion (n=5, 1 nmol/h ICV) for 12 days, followed by a 5-day recovery period. MC4-R activation transiently decreased food intake from 23±1 to 10±2 g/d. Despite the hypophagia, MC3/4-R activation increased MAP by 7±1 mm Hg. MC3/4-R inhibition for 12 days increased food intake from 21±1 to 35±4 g/d, decreased HR by 53±11 bpm, and caused no change in MAP despite the marked weight gain. In rats that were pair-fed to prevent increased food intake, MC3/4-R inhibition further decreased HR (-87±9 bpm), whereas MAP was unchanged. Thus, chronic hypothalamic MC3/4-R activation raises arterial pressure despite decreased food intake, whereas MC3/4-R inhibition causes marked weight gain without raising arterial pressure. These observations are consistent with the hypothesis that an intact hypothalamic MC3/4-R may be necessary for excess weight gain to raise arterial pressure.

Key Words: hypertension, receptors, melanocortin • blood pressure • heart rate • hypertension, experimental • obesity • insulin

This article has been cited by other articles:

				A. A. da Silva, J. M. do Carmo, B. Kanyicska, J. Dubinion, E. Brandon, and J. E. Hall Endogenous Melanocortin System Activity Contributes to the Elevated Arterial Pressure in Spontaneously Hypertensive Rats Hypertension, April 1, 2008; 51(4): 884 - 890. [Abstract] [Full Text] [PDF]

				M.-H. Tai, W.-T. Weng, W.-C. Lo, J. Y. H. Chan, C.-J. Lin, H.-C. Lam, and C.-J. Tseng Role of Nitric Oxide in {alpha}-Melanocyte-Stimulating Hormone-Induced Hypotension in the Nucleus Tractus Solitarii of the Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 455 - 461. [Abstract] [Full Text] [PDF]

				A. A. da Silva, L. S. Tallam, J. Liu, and J. E. Hall Chronic antidiabetic and cardiovascular actions of leptin: role of CNS and increased adrenergic activity Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1275 - R1282. [Abstract] [Full Text] [PDF]

				L. S. Tallam, A. A. da Silva, and J. E. Hall Melanocortin-4 Receptor Mediates Chronic Cardiovascular and Metabolic Actions of Leptin Hypertension, July 1, 2006; 48(1): 58 - 64. [Abstract] [Full Text] [PDF]

				A. A. da Silva, J. J. Kuo, L. S. Tallam, J. Liu, and J. E. Hall Does Obesity Induce Resistance to the Long-Term Cardiovascular and Metabolic Actions of Melanocortin 3/4 Receptor Activation? Hypertension, February 1, 2006; 47(2): 259 - 264. [Abstract] [Full Text] [PDF]

				L. S. Tallam, D. E. Stec, M. A. Willis, A. A. da Silva, and J. E. Hall Melanocortin-4 Receptor-Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia Hypertension, August 1, 2005; 46(2): 326 - 332. [Abstract] [Full Text] [PDF]

				L. S. Tallam, J. J. Kuo, A. A. da Silva, and J. E. Hall Cardiovascular, Renal, and Metabolic Responses to Chronic Central Administration of Agouti-Related Peptide Hypertension, December 1, 2004; 44(6): 853 - 858. [Abstract] [Full Text] [PDF]

				G. S. Gopalakrishnan, D. S. Gardner, S. M. Rhind, M. T. Rae, C. E. Kyle, A. N. Brooks, R. M. Walker, M. M. Ramsay, D. H. Keisler, T. Stephenson, et al. Programming of adult cardiovascular function after early maternal undernutrition in sheep Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R12 - R20. [Abstract] [Full Text] [PDF]

				A. A. da Silva, J. J. Kuo, and J. E. Hall Role of Hypothalamic Melanocortin 3/4-Receptors in Mediating Chronic Cardiovascular, Renal, and Metabolic Actions of Leptin Hypertension, June 1, 2004; 43(6): 1312 - 1317. [Abstract] [Full Text] [PDF]

				J. J. Kuo, A. A. da Silva, L. S. Tallam, and J. E. Hall Role of Adrenergic Activity in Pressor Responses to Chronic Melanocortin Receptor Activation Hypertension, February 1, 2004; 43(2): 370 - 375. [Abstract] [Full Text] [PDF]

				K. Rahmouni and W. G. Haynes Leptin and the Cardiovascular System Recent Prog. Horm. Res., January 1, 2004; 59(1): 225 - 244. [Abstract] [Full Text]