Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats.
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.
Morgan
D A
DA
Veterans Administration Medical Center, Department of Medicine, Iowa City, Iowa.
Thoren
P
P
Wilczynski
E A
EA
Victor
R G
RG
Mark
A L
AL
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
D010656:Phenylephrine; D012701:Serotonin; D010134:Fenclonine; D008784:Methysergide