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.