Cardiovascular effects of activation of central α7 and α4β2 nAChRs: a role for vasopressin in anaesthetized rats

Background and purpose: Central application of nicotine causes the release of vasopressin and affects blood pressure. Involvement of the 5 neuronal nicotinic receptor groups, α2*–α7* in these effects is unknown. The availability of selective agonists for α7 (PSAB‐OFP) and α4β2 (TC‐2559) nACh receptors allowed their role to be investigated. Experimental approach: Recordings were made of arterial blood pressure, heart rate and renal sympathetic nerve activity in anaesthetized male rats with neuromuscular blockade and artificial respiration. Effects of the agonists, PSAB‐OFP (1–10 μmol kg −1 ) and TC‐2559 (1–10 μmol kg −1 ) on these variables given intracerebroventricularly (i.c.v.) and intracisternally (i.c.) in the presence or absence of the antagonists, DhβE (10 μmol kg −1 ) and MLA (0.5 μmol kg −1 ), for the appropriate nicotinic receptor subtypes, respectively, and a V 1 receptor antagonist, given i.v. or centrally, were investigated. Key results : Both agonists given i.c.v. caused a delayed rise in blood pressure and renal nerve activity which could be blocked only with the appropriate antagonist. The agonists had an earlier onset of action when given i.c., favouring the brainstem as the major site of action. The effects of these agonists were also attenuated by the V 1 receptor antagonist given i.v. and blocked when this antagonist was given centrally. Antagonists had no effect on baseline variables. Conclusions and implications: Activation of α4β2 and α7 receptors in the brainstem is mainly responsible for the cardiovascular effects of activating these receptors, which have a similar profile of action. These actions, although independent, are mediated by the central release of vasopressin. British Journal of Pharmacology (2008) 153 , 1728–1738; doi: 10.1038/bjp.2008.47 ; published online 25 February 2008