Proceedings of The Physiological Society

Trinity College Dublin (2003) J Physiol 551P, C55


Role of central 5-HT7 as well as 5-HT1A receptors in cardiopulmonary reflex control in anaesthetised rats

Daniel O. Kellett, Andrew G. Ramage* and David Jordan

Departments of Physiology and *Pharmacology , UCL, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK

Central 5-hydroxytryptamine-containing neurones, via activation of 5-HT1A receptors, control parasympathetic outflow to the heart, airways (see Ramage, 2001) and bladder (Conley et al. 2001). Furthermore, blockade of central 5-HT7 receptors can inhibit the micturition reflex (Read et al., 2003). The present experiments compare the roles of central 5-HT7 and 5-HT1A receptors on the cardiopulmonary reflex, using the selective 5-HT7 receptor antagonist SB-269970 (Hagan et al. 2000) and the selective 5-HT1A receptor antagonist WAY-100635.

Male Sprague-Dawley rats (300-350 g) were anaesthetised with α-chloralose (80 mg kg-1 I.V. and maintained with 15 mg kg-1 when necessary), atenolol pretreated (1 mg kg-1 I.V.), neuromuscularly blocked (α-bungarotoxin 150 µg kg-1 I.V.; Jones et al. 2002), mechanically ventilated, and instrumented to record BP, phrenic (PNA) and renal nerve activity (RNA), and ECG (R-R interval). Depth of anaesthesia was assessed by the stability of BP, HR and PNA following a noxious stimulus. Cardiopulmonary afferents were stimulated by right atrial injection of phenylbiguanide (PBG; 3-15 µg kg-1). After three control reflexes, SB-269970 (30, 100, or 300 µg kg-1), WAY-100635 (100 µg kg-1), or saline was given intracisternally (10 µl over 20 s), and the reflex repeated after 5, 15, 25 and 35 min (Table 1). At the end of experiments, animals were killed by an overdose of pentobarbitone.

Neither drug significantly altered baseline BP, R-R interval or RNA, but after 15 min SB-269970 (300 µg kg-1) significantly inhibited PNA by 76 ± 12 %, and the reflex decrease in RNA by 97 ± 2 % (means ± S.E.M.).

These data demonstrate that both central 5-HT7 and 5-HT1A receptors are activated during the cardiopulmonary reflex to cause an increase in cardiac vagal outflow in anaesthetised rats.

D.O.K. is a BHF PhD student. We are grateful to GSK (UK) for the gift of SB-269970.

Where applicable, experiments conform with Society ethical requirements