Cardiovascular responses to microinjections of nicotine into the caudal ventrolateral medulla of the rat

This study focuses on the role of nicotinic receptors located in the caudal ventrolateral medullary depressor area (CVLM) in regulating/modulating car diovascular function. Blood pressure and heart rate were monitored by stand ard techniques in urethane-anesthetized, artificially ventilated, adult mal e Wistar rats. Multi-barreled glass-micropipettes (tip size 20-40 mum) were used to make microinjections (100 nl) into the CVLM. Concentrations of nic otine ranging from 250 muM to 10 mM were microinjected unilaterally into th e CVLM. The maximum depressor and bradycardic responses were elicited by a 1 mM concentration of nicotine. Sequential microinjections of mecamylamine (1 mM), an antagonist for nicotinic receptors containing alpha3 beta4 subun its, then alpha -bungarotoxin (1 muM), an antagonist for nicotinic receptor s containing alpha -7 subunits, were made into the CVLM. Microinjecting a c ombination of a nicotinic receptor blocker and toxin resulted in the comple te blockade of the cardiovascular responses induced by nicotine (1 mM, 100 nl). These results indicate that: (1) nicotinic receptors are present in th e CVLM; (2) activation of these receptors results in depressor and bradycar dic responses; (3) for a complete blockade of nicotine-induced cardiovascul ar responses, it is necessary to use a combination of mecamylamine and alph a -bungarotoxin; (4) since mecamylamine and alpha -bungarotoxin are known t o block nicotinic receptors containing alpha3 beta4 and alpha -7 subunits, respectively, two different subtypes of nicotinic receptors (one which cont ains a combination of alpha3 beta4 subunits, and one which contains alpha - 7 subunits) must be present in the CVLM; and (5) it is not clear whether th ese two subtypes of nicotinic receptor are located on the same or different populations of CVLM-neurons. (C) 2001 Elsevier Science B.V. All rights res erved.