Cardiovascular effects of melanin-concentrating hormone.

Melanin-concentrating hormone (MCH) is a cyclic 19-amino acid neuropeptide exclusively synthesized in the lateral hypothalamic area (LHA) and the zona incerta (ZI) that has been implicated in the regulation of energy balance. Despite what is known about the orexigenic effect of MCH, whether MCH has distinct cardiovascular and metabolic effects has yet to be determined. Thus, our goal here was to characterize the concurrent cardiovascular, metabolic, and behavioral responses of male rats to chronic intracerebroventricular (icv) infusion of MCH. Male Long-Evans rats were instrumented with telemetry transmitters for measurement of heart rate (HR) and housed in room calorimeters for assessment of food intake and oxygen consumption (VO(2)) at standard lab ambient temperature (23 degrees C) in order to examine physiological responses to chronic infusion of MCH (8 microg/d and 16 microg/d). Our findings provide the first evidence that chronic administration of MCH induces bradycardia and reduced mean arterial pressure, while it did not affect VO(2). A second experiment was performed in which the physiological responses to an acute icv infusion of MCH were observed. The results of experiment 2 indicate that MCH leads to a low HR that is maintained during the first 2 h post-infusion, the time period during which MCH acutely stimulated feeding. Collectively, these findings confirm that MCH may be an important modulator of sympathetic nervous system activity and thus may play a critical role in coordinating normal responses to negative energy balance.

Estradiol decreases the orexigenic effect of melanin-concentrating hormone in ovariectomized rats.

Estradiol exerts an inhibitory effect on food intake via interactions with anorexigenic peptides, like cholecystokinin, that function to decrease meal size. It is currently unknown whether estradiol also interacts with orexigenic compounds implicated in the physiological control of food intake. Thus, the primary goal of this study was to determine whether estradiol decreases the orexigenic effect of melanin-concentrating hormone (MCH), a neuropeptide that, like estradiol, appears to influence food intake by selectively affecting the controls of meal size. Food and water intake were monitored following lateral ventricular (icv) infusions of 5 mug MCH or saline vehicle in oil- and estradiol-treated ovariectomized rats. MCH increased food intake throughout the first 4 h of the dark phase in oil-treated rats, but only for the last 2 h of the same 4-h interval in estradiol-treated rats. As a result, the orexigenic effect of MCH was significantly lower in estradiol-treated rats, relative to oil-treated rats. During this interval of MCH-stimulated feeding, a prandial increase in water intake was not observed in either oil- or estradiol-treated rats. We conclude that estradiol decreases the orexigenic effect of MCH in ovariectomized rats.

Perinatal MSG treatment attenuates fasting-induced bradycardia and metabolic suppression.

We studied the effect of arcuate nucleus (ARC) lesions induced pharmacologically by the perinatal treatment of monosodium l-glutamate (MSG) on the cardiovascular, metabolic, and behavioral responses to fasting. Saline and MSG-treated male Sprague-Dawley rats were instrumented with telemetry devices for measurement of mean arterial pressure (MAP) and heart rate (HR) and housed in room calorimeters at an ambient temperature (T(a)) of 23 degrees C for assessment of oxygen consumption (VO(2)). At baseline, controls and MSG-treated rats had similar MAP (control=95+/-4; MSG=91+/-2 mmHg), HR (control=323+/-4; MSG=324+/-2 bpm), and VO(2) (control=8.7+/-0.3; MSG=8.6+/-0.2 ml/min). There were no differences in fasting-induced reductions in body weight or in food intake upon refeeding. MSG-treatment significantly attenuated fasting-induced reductions in HR and VO(2). This effect was specific to reduced caloric availability, as MSG-treated rats exhibited intact capacity to both increase and decrease HR and VO(2) in response to cold (T(a)=15 degrees C) and to thermoneutrality (T(a)=30 degrees C). Additional studies were performed in saline- and MSG-treated rats chronically treated with beta(1)-adrenergic receptor blockade (atenolol) prior to and during fasting. In controls, the cardiovascular responses to fasting during beta(1)-blockade were blunted and generally mimicked the effects of MSG-treatment, while beta(1)-blockade had no additional effect on MSG-treated rats. The results are consistent with the hypothesis that ARC neuronal signaling is requisite for intact homeostatic responses to fasting and may participate in fasting-induced withdrawal of cardiac sympathetic activity.