Intrathecal neuromedin U induces biphasic effects on sympathetic vasomotor tone, increases respiratory drive and attenuates sympathetic reflexes in rat.

BACKGROUND: Neuromedin U (NMU) is a brain-gut peptide that plays regulatory roles in feeding, anxiety, smooth muscle contraction, blood flow, pain and adrenocortical function via two receptors, the NMU receptor 1 and NMU receptor 2. NMU has several known functions in the periphery, but its role in central cardiorespiratory regulation remains poorly understood. EXPERIMENTAL APPROACH: Experiments were conducted on urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats (n= 42) to determine if NMU modulates sympathetic vasomotor output at the spinal level or modulates baro-, chemo- and somato-sympathetic reflexes. KEY
RESULTS: Intrathecal (i.t.) injections of NMU (2.5-20 nmol) caused a dose-dependent biphasic response, initially a brief period of hypertension and sympatho-excitation followed by prolonged hypotension and sympatho-inhibition. Peak excitatory as well as inhibitory responses were observed at 20 nmol. NMU (20 nmol) initially increased mean arterial pressure and splanchnic sympathetic nerve activity by 24 mmHg and 27% and then reduced these by 37 mmHg and 47%, respectively. NMU also dose-dependently increased respiratory drive, as indicated by a rise in phrenic nerve amplitude, an increase in neural minute ventilation and a shortening of the inspiratory period. Both sympatho-excitatory peaks of the somato-sympathetic reflex were abolished by i.t. NMU. Pressor, sympatho-excitatory and tachycardiac responses to chemoreceptor activation (100% N₂) were blocked or significantly reduced following i.t. NMU. NMU also reduced barosensitivity.
CONCLUSIONS: The data demonstrate that NMU, acting in the spinal cord, differentially contributes to the control of sympathetic tone and adaptive sympathetic reflexes.