title: Neuromedin U causes biphasic cardiovascular effects and impairs baroreflex function in rostral ventrolateral medulla of spontaneously hypertensive rat.
abstract: Neuromedin U (NMU) causes biphasic cardiovascular and sympathetic responses and attenuates adaptive reflexes in the rostral ventrolateral medulla (RVLM) and spinal cord in normotensive animal. However, the role of NMU in the pathogenesis of hypertension is unknown. The effect of NMU on baseline cardiorespiratory variables in the RVLM and spinal cord were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Experiments were also conducted to determine the effects of NMU on somatosympathetic and baroreceptor reflexes in the RVLM of SHR and WKY. NMU injected into the RVLM and spinal cord elicited biphasic response, a brief pressor and sympathoexcitatory response followed by a prolonged depressor and sympathoinhibitory response in both hypertensive and normotensive rat models. The pressor, sympathoexcitatory and sympathoinhibitory responses evoked by NMU were exaggerated in SHR. Phrenic nerve amplitude was also increased following intrathecal or microinjection of NMU into the RVLM of both strains. NMU injection into the RVLM attenuated the somatosympathetic reflex in both SHR and WKY. Baroreflex sensitivity was impaired in SHR at baseline and further impaired following NMU injection into the RVLM. NMU did not affect baroreflex activity in WKY. The present study provides functional evidence that NMU can have an important effect on the cardiovascular and reflex responses that are integrated in the RVLM and spinal cord. A role for NMU in the development and maintenance of essential hypertension remains to be determined.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2112, Australia.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Rahman
authors.forename: Israt Z
authors.initials: IZ
authors.lastname: Shahid
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
mesh_terms: D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D006339:Heart Rate; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000503:physiopathology*; D009479:Neuropeptides / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D009479:Neuropeptides; C056900:neuromedin U