Published Online
on January 5, 2004

A more recent version of this article appeared on February 1, 2004

This Article Full Text (PDF) All Versions of this Article: 43/2/370    most recent 01.HYP.0000111836.54204.93v1 Alert me when this article is cited Alert me if a correction is posted 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. Related Collections Obesity

Submitted on September 30, 2003
Revised on October 30, 2003

Role of Adrenergic Activity in Pressor Responses to Chronic Melanocortin Receptor Activation

Jay J. Kuo^*; Alexandre A. da Silva; Lakshmi S. Tallam; and John E. Hall

From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.

^* To whom correspondence should be addressed. E-mail: jkuo{at}physiology.umsmed.edu.

Abstract--Acute studies have shown that MC3/4-R stimulation increases sympathetic activity, but the role of adrenergic activation in mediating the cardiovascular and renal responses to chronic melanocortin 3- and 4-receptor (MC3/4-R) activation is unknown. The present study tested whether chronic MC3/4-R activation raises blood pressure and whether these changes are attenuated by ₁+-adrenergic blockade. Rats were instrumented with an intracerebroventricular (ICV) cannula and arterial and venous catheters for measurements of mean arterial pressure (MAP) and heart rate (HR) 24 hours per day, and intravenous infusions. After control measurements, rats were intravenously infused with either saline vehicle (n=7) or ₁+ -adrenergic antagonists (n=6, terazosin+propranolol, 10 mg/kg per day each) for 21 days. Five days after starting the vehicle or adrenergic blockade, the MC3/4-R agonist, MTII (10 ng/h), was infused ICV for 11 days followed by a 5-day recovery period. Another group of rats was infused with the adrenergic antagonists for 21 days but received the saline vehicle ICV for 11 days (n=7). MC3/4-R activation decreased food intake from 21±1 to 8±2 g/d by day 3 of MC3/4-R activation, and increased MAP and HR by an average of 8±2 mm Hg and 9±5 bpm, respectively. Adrenergic blockade did not alter the MC3/4-R-mediated decrease in food intake but abolished the increases in MAP and HR (1±2 mm Hg and -12±5 bpm, respectively, compared with control). ICV vehicle infusion during adrenergic blockade did not alter food intake or MAP. Glomerular filtration rate was unchanged in both the vehicle-infused and adrenergic blocked rats during MC3/4-R activation. These results indicate that the chronic actions of MC3/4-R activation on MAP and HR are mediated by adrenergic activation.

Key words: sympathetic nervous system • blood pressure • obesity

This article has been cited by other articles:

				A. A. da Silva, J. M. do Carmo, J. N. Freeman, L. S. Tallam, and J. E. Hall A Functional Melanocortin System May Be Required for Chronic CNS-Mediated Antidiabetic and Cardiovascular Actions of Leptin Diabetes, August 1, 2009; 58(8): 1749 - 1756. [Abstract] [Full Text] [PDF]

				N. Balthasar Feeding signals to the hungry mind Exp Physiol, August 1, 2009; 94(8): 857 - 866. [Abstract] [Full Text] [PDF]

				J. R. Greenfield, J. W. Miller, J. M. Keogh, E. Henning, J. H. Satterwhite, G. S. Cameron, B. Astruc, J. P. Mayer, S. Brage, T. C. See, et al. Modulation of Blood Pressure by Central Melanocortinergic Pathways N. Engl. J. Med., January 1, 2009; 360(1): 44 - 52. [Abstract] [Full Text] [PDF]

				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]

				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]