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 cardiovascular function. Blood pressure and heart rate were monitored by standard techniques in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Multi-barreled glass-micropipettes (tip size 20-40 mum) were used to make microinjections (100 nl) into the CVLM. Concentrations of nicotine ranging from 250 muM to 10 mM were microinjected unilaterally into the 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 subunits, then alpha -bungarotoxin (1 muM), an antagonist for nicotinic receptors containing alpha -7 subunits, were made into the CVLM. Microinjecting a combination of a nicotinic receptor blocker and toxin resulted in the complete blockade of the cardiovascular responses induced by nicotine (1 mM, 100 nl). These results indicate that: (1) nicotinic receptors are present in the CVLM; (2) activation of these receptors results in depressor and bradycardic responses; (3) for a complete blockade of nicotine-induced cardiovascular responses, it is necessary to use a combination of mecamylamine and alpha -bungarotoxin; (4) since mecamylamine and alpha -bungarotoxin are known to block nicotinic receptors containing alpha3 beta4 and alpha -7 subunits, respectively, two different subtypes of nicotinic receptors (one which contains 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 these two subtypes of nicotinic receptor are located on the same or different populations of CVLM-neurons. (C) 2001 Elsevier Science B.V. All rights reserved.