Role of adrenergic activity in pressor responses to chronic melanocortin receptor activation.

Hypertension

Department of Physiology and Biophysics, 2500 N State St, University of Mississippi Medical Center, Jackson, MS 39216, USA.

Published: February 2004

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 alpha1+beta-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 alpha1+ beta-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.

Download full-text PDF

Source
http://dx.doi.org/10.1161/01.HYP.0000111836.54204.93DOI Listing

Publication Analysis

Top Keywords

mc3/4-r activation
24
adrenergic blockade
12
food intake
12
activation
9
role adrenergic
8
responses chronic
8
chronic melanocortin
8
mc3/4-r
8
adrenergic activation
8
saline vehicle
8

Similar Publications

Previous studies suggest that activation of the CNS melanocortin system reduces appetite while increasing sympathetic activity and arterial pressure. The present study tested whether endogenous activity of the CNS melanocortin 3/4 receptors (MC3/4-R) contributes to elevated arterial pressure in the spontaneously hypertensive rat (SHR), a model of hypertension with increased sympathetic activity. A cannula was placed in the lateral ventricle of male SHR and Wistar (WKY) rats for chronic intracerebroventricular (ICV) infusions (0.

View Article and Find Full Text PDF

Objective: Melanocyte-stimulating hormone (MSH) peptides processed from proopiomelanocortin (POMC) regulate energy homeostasis by activating neuronal melanocortin receptor (MC-R) signaling. Agouti-related peptide (AgRP) is a naturally occurring MC-R antagonist but also displays inverse agonism at constitutively active melanocortin-4 receptor (MC4-R) expressed on transfected cells. We investigated whether AgRP functions similarly in vivo using mouse models that lack all neuronal MSH, thereby precluding competitive antagonism of MC-R by AgRP.

View Article and Find Full Text PDF

MTII attenuates ghrelin- and food deprivation-induced increases in food hoarding and food intake.

Horm Behav

December 2007

Department of Biology and Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30302-4010, USA.

Food deprivation triggers a constellation of physiological and behavioral changes including increases in peripherally-produced ghrelin and centrally-produced agouti-related protein (AgRP). Upon refeeding, food intake is increased in most species, however hamsters primarily increase food hoarding. Food deprivation-induced increases in food hoarding by Siberian hamsters are mimicked by peripheral ghrelin and central AgRP injections.

View Article and Find Full Text PDF

Does obesity induce resistance to the long-term cardiovascular and metabolic actions of melanocortin 3/4 receptor activation?

Hypertension

February 2006

Department of Physiology and Biophysics, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS 9216-4505, USA.

Previous studies suggest that blockade of melanocortin 3 and 4 receptors (MC3/4-R) markedly attenuates the chronic hypertensive effects of leptin. Although obesity has been reported to be associated with leptin "resistance," it is unclear whether obesity alters the cardiovascular and metabolic effects of chronic MC3/4-R activation. Therefore, we tested whether the cardiovascular and metabolic actions of MC3/4-R activation are attenuated in Sprague-Dawley rats fed a high-fat diet (HF, n=6) compared with rats fed a standard chow (NF, n=6) for 12 months.

View Article and Find Full Text PDF

The present study aims to elucidate whether the central melanocortin receptors [melanocortin-3 and -4 receptors (MC3/4-R)] are involved in regulating GnRH pulse generator activity in female goats. The GnRH pulse generator activity was electrophysiologically assessed at the intervals of characteristic increases in multiple-unit activity (MUA volleys) in the mediobasal hypothalamus. In ovariectomized goats, all doses (0.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!