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

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.

Noxious somatic stimuli diminish respiratory-sympathetic coupling by selective resetting of the respiratory rhythm in anaesthetized rats.

Noxious somatic stimulation evokes respiratory and autonomic responses. The mechanisms underlying the responses and the manner in which they are co-ordinated are still unclear. The effects of activation of somatic nociceptive fibres on lumbar sympathetic nerve activity at slow (2-10 Hz) and fast frequency bands (100-1000 Hz) and the effects on respiratory-sympathetic coupling are unknown. In anaesthetized, artificially ventilated Sprague-Dawley rats under neuromuscular blockade, ensemble averaging of sympathetic activity following high-intensity single-pulse stimulation of the sciatic nerve revealed two peaks (~140 and ~250 ms) that were present at similar latencies whether or not slow or fast band filtering was used. Additionally, in the slow band of both lumbar and splanchnic sympathetic nerve activity, a third peak with a very slow latency (~650 ms) was apparent. In the respiratory system, activation of the sciatic nerve decreased the expiratory period when the stimulus occurred during the first half of expiration, but increased the expiratory period if the stimulus was delivered in the second half of the expiratory phase. The phase shifting of the respiratory cycle also impaired the respiratory-sympathetic coupling in both splanchnic and lumbar sympathetic nerve activity in the subsequent respiratory cycle. The findings suggest that noxious somatosympathetic responses reduce the co-ordination between respiration and perfusion by resetting the respiratory pattern generator.