Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats

• ICV injections of 5-HT did not affect arterial blood pressure of conscious rats.
• ICV 5-HT elicited dramatic changes in systemic hemodynamics.
• ICV 5-HT increased mesenteric vascular resistance but decreased hindquarter resistance.
• All effects of ICV 5-HT were prevented by ICV injection of a 5-HT1/5-HT2-receptor antagonist.
• Nitric oxide synthase inhibition markedly affected the hemodynamic effects of ICV 5-HT.

The aims of this study were to determine (i) the effects of intracerebroventricular (i.c.v.) injections of 5-hydroxytryptamine (5-HT, 10 μg) 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 20 min. 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 25–35 min. 5-HT also produced a transient decrease in RR (− 26 ± 8% at 10 min). All of these responses were prevented by the prior i.c.v. injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (10 μg). The intravenous injection of the NO synthesis inhibitor, L-NAME (25 μmol/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.