Nicotine's central cardiovascular actions: receptor subtypes involved and their possible physiological role in anaesthetized rats.

摘要

Centrally applied nicotine causes changes in blood pressure and vasopressin release. The involvement of different neuronal nicotinic receptor subtypes in these actions was investigated in anaesthetized rats. Nicotine administered i.c.v. caused a dose-related increase in blood pressure and renal sympathoinhibition, while i.c. administration also caused a bradycardia. In the presence of the V(1A) receptor antagonist (i.v.), nicotine (i.c) now caused a depressor response along with sympathoinhibition and bradycardia. Nicotine (0.3 mumol/kg; i.c.v.) in the presence of the alpha4beta2 receptor antagonist, dihydro-beta-erythroidine, (i.c.v.) evoked renal sympathoexcitation, while the alpha7 receptor antagonist, methyllycaconitine, delayed the expected sympathoinhibition. Both receptor antagonists blocked the pressor response. Dihydro-beta-erythroidine (i.c., 10mumol/kg) alone caused a transient pressor response and increased renal nerve activity. Methyllycaconitine (i.c., 0.1 mumol/kg) alone caused a slow fall in blood pressure and renal nerve activity, while the higher doses caused a pressor response and increased renal nerve activity. It was concluded that for nicotine to release vasopressin, activation of both alpha4beta2 and alpha7 receptors is required. The ability of nicotine to cause sympathoinhibition is mediated by beta4*-containing receptors, possibly alpha3beta4 receptors, and that activation of these receptors can override the sympathoexcitatory action of alpha4beta2 and alpha7 receptors. The ability of dihydro-beta-erythroidine and high doses of methyllycaconitine i.c. to cause sympathoexcitation and a pressor response is due to receptor antagonists blocking these sympathoinhibitory beta4*-containing receptors, which receive a tonic cholinergic input. As the low dose of methyllycaconitine caused sympathoinhibition, this indicates that sympathoexcitatory alpha7 receptors also receive a tonic input.