Intrathecal melanin-concentrating hormone reduces sympathetic tone and blocks cardiovascular reflexes

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide that acts to increase feeding behavior and decrease energy expenditure. The role of MCH in central cardiorespiratory regulation is still poorly understood. Experiments were conducted on urethane-anesthetized, vagotomized, and artificially ventilated male Sprague-Dawley rats (n = 22) to ascertain whether MCH modulates sympathetic vasomotor tone, as well as barosympathetic, chemosympathetic, and somatosympathetic reflexes at the level of the spinal cord. Intrathecal injection of 10 μl of MCH produced a dose-dependent hypotension, bradycardia, and sympathoinhibition. Peak response was observed following administration of 1 mM MCH, causing a decrease in mean arterial pressure of 39 ± 2 mmHg (P < 0.001), splanchnic sympathetic nerve activity of 78 ± 11% (P < 0.001), and heart rate of 87 ± 11 beats per minute (bpm) (P < 0.01). The two peaks of the somatosympathetic reflex were decreased by intrathecal MCH, 7 ± 3% (P < 0.01) and 31 ± 6% (P < 0.01), respectively, and the spinal component of the reflex was accentuated 96 ± 23% (P < 0.05), with respect to the baseline for MCH, compared with the two peaks and spinal component of the somatosympathetic reflex elicited following saline injection with respect to the baseline for saline. MCH decreased the sympathetic gain to 120 s of hyperoxic hypercapnea (10% CO(2) in 90% O(2)) and to 10-12 s poikilocapneic anoxia (100% N(2)) from 0.74 ± 0.14%/s to 0.23 ± 0.04%/s (P < 0.05) and 16.47 ± 3.2% to 4.35 ± 1.56% (P < 0.05), respectively. There was a 34% decrease in gain and a 62% decrease in range of the sympathetic baroreflex with intrathecal MCH. These data demonstrate that spinal MCH blunts the central regulation of sympathetic tone and adaptive sympathetic reflexes.