Cardiovascular effects of activation of central alpha7 and alpha4beta2 nAChRs: a role for vasopressin in anaesthetized rats.
OBJECTIVE
Central application of nicotine causes the release of vasopressin and affects blood pressure. Involvement of the 5 neuronal nicotinic receptor groups, alpha2(*)-alpha7(*) in these effects is unknown. The availability of selective agonists for alpha7 (PSAB-OFP) and alpha4beta2 (TC-2559) nACh receptors allowed their role to be investigated.


METHODS
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 micromol kg(-1)) and TC-2559 (1-10 micromol kg(-1)) on these variables given intracerebroventricularly (i.c.v.) and intracisternally (i.c.) in the presence or absence of the antagonists, DhbetaE (10 micromol kg(-1)) and MLA (0.5 micromol kg(-1)), for the appropriate nicotinic receptor subtypes, respectively, and a V(1) receptor antagonist, given i.v. or centrally, were investigated.


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
Activation of alpha4beta2 and alpha7 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.
Moore
C
C
Department of Pharmacology, University College London, London, UK.
Wang
Y
Y
Ramage
A G
AG
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014667:Vasopressins / Q000187:drug effects / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C472510:5'-phenylspiro(1-azabicyclo(2.2.2.))octane-3,2'-(3'H)furo(2,3-b)pyridine; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C419442:TC 2559; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D014667:Vasopressins; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D000157:Aconitine