title: Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats.
abstract: The aims of this study were to determine (i) the effects of intracerebroventricular (i.c.v.) injections of 5-hydroxytryptamine (5-HT, 10μg) on mean arterial blood pressure (MAP), heart rate (HR) and mesenteric (MR), renal (RR) and hindquarter (HQR) vascular resistances of conscious rats, (ii) the central 5-HT receptor subtype which mediates these effects, and (iii) the role of nitric oxide (NO) in the expression of these responses. The i.c.v. injection of 5-HT had minor effects on MAP but produced a decrease in HR (-18±4%), which lasted for 20min. The i.c.v. injection of 5-HT elicited marked increases in MR (+50±7%) and reductions in HQR (-31±3%). These responses occurred promptly and lasted for 25-35min. 5-HT also produced a transient decrease in RR (-26±8% at 10min). All of these responses were prevented by the prior i.c.v. injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (10μg). The intravenous injection of the NO synthesis inhibitor, L-NAME (25μmol/kg), produced a sustained pressor response, bradycardia and increases in MR, RR and HQR. Subsequent i.c.v. injection of 5-HT produced a minor pressor response (+7±2%), bradycardia (-18±3%), an increase in MR (+52±8%) but no decreases in RR or HQR. This study demonstrates that i.c.v. 5-HT differentially affects peripheral vascular resistances by activation of central 5-HT1/5-HT2-receptors. It appears that L-NAME did not interfere with the central actions of 5-HT as it did not prevent the 5-HT-induced bradycardia or mesenteric vasoconstriction. Since the 5-HT-induced falls in RR and HQR were abolished by L-NAME, it is possible that these responses are mediated by an active neurogenic process involving the release of NO within the vasculature.
authors.affiliation: Departments of Biomedical Sciences (College of Veterinary Medicine), Ithaca, NY, USA; Cell and Developmental Biology (Weil Cornell Medical College), New York, NY, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Davisson
authors.affiliation: Department of Anesthesia, University of Iowa, Iowa City, IA, USA.
authors.forename: James N
authors.initials: JN
authors.lastname: Bates
authors.affiliation: Departments of Psychology, The University of lowa, Iowa City, IA, USA; Departments of Health and Human Physiology, The University of lowa, Iowa City, IA, USA; Departments of Pharmacology, The University of lowa, Iowa City, IA, USA; The Francois M. Abboud Cardiovascular Research Center, The University of lowa, Iowa City, IA, USA.
authors.forename: Alan Kim
authors.initials: AK
authors.lastname: Johnson
authors.affiliation: Departments of Pediatrics and Pharmacology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: sjl78@case.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb; D007276:Injections, Intraventricular; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012079:Renal Circulation / Q000187:drug effects*; D012701:Serotonin / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D012701:Serotonin; D019001:Nitric Oxide Synthase
keywords: 5-HT(1)/5-HT(2)-receptors; 5-Hydroxytryptamine (5-HT); Arterial blood pressure; Conscious rats; Heart rate; Intracerebroventricular; Methysergide; Nitric oxide; Regional vascular blood flows; Regional vascular resistances