Central 5-HT _1Aand 5-HT₇ receptors contribute to reflex activation of parasympathetic outflow to the heart in anaesthetised rats (Kellett et al. 2003, 2004), but the origin of the 5-HT containing fibres involved in this effect is not known.

Male Sprague-Dawley rats (300-350 g) were pretreated with either the tryptophan hydroxylase inhibitor para-chlorophenylalanine methyl ester (p-CPA; 350 mg kg^-1 i.p.) or saline (3.5 ml kg^-1 i.p.) for 2 days. On day 3 they were anaesthetised with a -chloralose (80 mg kg^-1 i.v. ), atenolol pretreated (1 mg kg^-1 i.v.), neuromuscularly blocked ( a -bungarotoxin 150 µg kg^-1 i.v.), ventilated, and instrumented to record arterial blood pressure (BP) and ECG (R-R interval). Cardiopulmonary afferents were stimulated with phenylbiguanide (2.5µg i.a.) and baroreceptors by raising BP with phenylephrine (10 µg i.v.). Baseline and reflex-evoked changes were measured, and baroreflex gain was calculated (Su et al. 1992). At the end of experiments, animals were transcardially perfuse-fixed and the medulla immunostained for 5-HT.

Pretreatment with p-CPA virtually abolished 5-HT immunoreactivity in cardiovascular areas of the medulla, but not in raphe cell bodies. 5-HT depleted animals had significantly lower baseline BP, and significantly smaller cardiopulmonary reflex bradycardia and baroreflex gain (see Table 1).

Table 1. Baseline and reflex-evoked variables in control and depleted rats. (Mean ± s.e.m.) * P<0.05, ** P<0.01, Student’s t-test relative to control.

These data suggest that endogenous 5-HT is required for full function of the bradycardic components of the cardiopulmonary and baroreflexes. The possibility cannot be excluded, however, that lack of endogenous 5-HT leads to a deeper plane of anaesthesia, which is presenting as lowered BP and blunted reflexes.

Kellett, DO et al.(2003). J.Physiol 551P, C55
Kellett, DO et al. (2004). J.Physiol 555P, C25
Su, DF et al. (1992). Clin.Exp.Pharmacol.Physiol 19, 767-776

D.O.K is a BHF Ph.D Student