title: Intrathecal neuromedin U induces biphasic effects on sympathetic vasomotor tone, increases respiratory drive and attenuates sympathetic reflexes in rat.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors.forename: A A
authors.initials: AA
authors.lastname: Rahman
authors.forename: I Z
authors.initials: IZ
authors.lastname: Shahid
authors.forename: P M
authors.initials: PM
authors.lastname: Pilowsky
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
chemical_list: D009479:Neuropeptides; C056900:neuromedin U