title: NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex.
abstract: The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5-11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O(2))11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O(2))11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.
authors.affiliation: Hypertension and Stroke Research Laboratory, Department of Physiology, University of Sydney, New South Wales, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Makeham
authors.forename: Ann K
authors.initials: AK
authors.lastname: Goodchild
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
mesh_terms: D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004566:Electrodes; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D064729:Neurokinin-1 Receptor Antagonists; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013152:Splanchnic Circulation / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000731:Androstanes; D001562:Benzimidazoles; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C086111:WIN 51708