title: Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats.
abstract: Hemorrhage in rats produces reflex decreases in heart rate (HR) and renal sympathetic nerve activity (RSNA). Because serotonergic antagonists attenuate hemorrhage-induced vagal-mediated bradycardia, we determined whether blockade of serotonin synthesis by p-chlorophenylalanine (PCPA) or of serotonin receptors with methysergide would also abolish the renal sympathoinhibition. Mean arterial pressure (MAP), HR, and RSNA were recorded in chloralose-anesthetized rats pretreated with PCPA (300 mg.kg-1.day-1 X 3 days ip, n = 12) or vehicle (0.3 ml saline, n = 9). During hemorrhage, where MAP was maintained at 50 mmHg for 8 min, vehicle-treated rats decreased HR by 27 +/- 13 beats/min and RSNA by -55 +/- 7%. In PCPA-treated rats, HR and RSNA did not change. Cervical vagotomy abolished the bradycardia and sympathoinhibition during hemorrhage. After acute administration of methysergide (400 micrograms/kg iv, n = 8) hemorrhage produced increases of RSNA, whereas vehicle (0.5 ml saline, n = 7) preserved the renal sympathoinhibition to hemorrhage in conscious rats. Finally, volume expansion (0.88 ml blood/100 g body wt) produced comparable decreases in RSNA in sinoaortic-denervated rats pretreated with PCPA (n = 11) or vehicle (n = 10) (-58 +/- 9 vs. 47 +/- 7%, respectively). We conclude that serotonergic mechanisms are critically involved in vagal afferent inhibition of RSNA during severe hemorrhage in rats.
authors.affiliation: Veterans Administration Medical Center, Department of Medicine, Iowa City, Iowa.
authors.forename: D A
authors.initials: DA
authors.lastname: Morgan
authors.forename: P
authors.initials: P
authors.lastname: Thoren
authors.forename: E A
authors.initials: EA
authors.lastname: Wilczynski
authors.forename: R G
authors.initials: RG
authors.lastname: Victor
authors.forename: A L
authors.initials: AL
authors.lastname: Mark
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D008784:Methysergide / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000502:physiology*; D012850:Sinus of Valsalva / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000502:physiology / Q000503:physiopathology*; D009435:Synaptic Transmission; D014628:Vagotomy
chemical_list: D010656:Phenylephrine; D012701:Serotonin; D010134:Fenclonine; D008784:Methysergide