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(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

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