EFFECTS OF NICOTINE ON BRAIN-STEM MECHANISMS OF CARDIOVASCULAR CONTROL

The role of the central nervous system in the pressor effect of nicoti ne is not well understood. In this study, we evaluated the cardiovascu lar effects of nicotine in the lower brainstem of normotensive and hyp ertensive rats. Microinjection of nicotine (0.012-3696 pmol/60 nl) int o the nucleus of the solitary tract and area postrema of Sprague-Dawle y (SD), Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) d ecreased blood pressure and heart rate. In contrast, administration of similar doses of nicotine within the rostral ventrolateral medulla (R VLM) evoked a long-lasting pressor and tachycardic effect. This presso r effect was completely abolished by prior microinjection of hexametho nium. In SHR the depressor and bradycardic responses in the nucleus of the solitary tract and area postrema were similar to those of normote nsive animals. The pressor effect in the RVLM, however, was more prono unced in the SHR than in WKY or SD rats. In additional experiments, th e changes produced by intra-RVLM administration of nicotine on renal s ympathetic nerve activity, blood pressure and heart rate were evaluate d before and after equidepressor intravenous doses of either clonidine , labetalol or prazosin. The prior administration of labetalol antagon ized the pressor effect of nicotine in the three strains of rats (SHR, 82 +/- 6%; SD, 96 +/- 4%; WKY, 83 +/- 9%). Prazosin inhibited the nic otine pressor response by 69% in SHR, by 44% in SD and by 70% in WKY. Clonidine had no effect on nicotine response in the three groups of ra ts. In conclusion, nicotine administration within the RVLM increases r enal sympathetic nerve activity and blood pressure. The pressor respon se seems to be greater in SHR than in normotensive rats, and adrenocep tor blockade but not equidepressor doses of clonidine can attenuate th is response. These findings suggest a role for medullary cholinergic r eceptors in the cardiovascular sympathetic-mediated effects of smoking .