Cardiovascular effects of central α7 nicotinic receptors are mediated by vasopressinergic pathways in anaesthetized rats

Christopher Moore1, Yun Wang2 & Andrew G Ramage, 1Department of Pharmacology, UCL, London NW3 2PF, 2Lilly Research Centre, Eli Lilly Co. & Ltd, Windlesham, Surrey, UK.

Activation of central nicotinic receptors causes a rise in blood pressure due to the release of vasopressin (Moore et al. 2004). However, there is no information as to whether this release of vasopressin is central and/or peripheral. Hence the role of central and/or peripheral released vasopressin in the cardiovascular effects evoked by the α7 nicotinic receptor agonist (PSAB-OFP, Broad et al., 2002) and the α 4β2 nicotinic receptor agonist TC-2559 given i.c.v. or i.c. were examined.

Male Sprague Dawley rats (250-350g) were anaesthetized ( i.v.) with α -chloralose (100 mg kg -1 and maintained with 15 mg kg -1 when necessary), artificially ventilated and neuromuscular blocked (3 mg kg -1; decamethonium). Recordings were made of MAP, HR and renal nerve activity (RNA). Depth of anaesthesia was assessed by the stability of MAP, HR and RNA following a noxious stimulus. Changes were compared with control, saline (5 µl; i.c.v.) in the presence of the V1 receptor antagonist (i.c.v. & i.c.) by two-way ANOVA and the least significant difference test. All values are means ± S.E.M. At the end of the experiment animals were killed by an overdose of pentobarbitone.

PSAB-OFP (Astra IV; 3 µmol kg -1) given i.c.v. (n=5) and i.c. (n=5) evoked a significantly increased mean arterial blood pressure (MAP; 26±7 & 38 ± 8 mmHg) and renal nerve activity (RNA; 126±23 & 130 ± 30%). In the presence of a V1 receptor antagonist (0.03 μg kg -1; n=5; Moore et al. 2004) i.c.v. or i.c. these effects on MAP were blocked although in both there was now a delayed fall in MAP. Further, the increase in RNA were also blocked, although for i.c. PSAB-OFP there was a significant increases at 1 min of 48±18%. TC-2559 (3 µmol kg-1) given i.c.v. (n=5) and i.c. (n=5) also evoked a significantly increased mean arterial blood pressure (MAP; 22±3 & 21 ± 7 mmHg) and renal nerve activity (RNA; 249±53 & 86 ± 28%). Again in the presence of a V1 receptor antagonist i.c.v. & i.c. the rise in MAP and RNA were blocked although again i.c. TC-2559 cause a transient rise in RNA after 1 min. There was no evidence that V1 antagonist had leaked out of the brain as the pressor response to i.v. vasopressin was unaffected

These data indicate that activation of α7 and α4 β2 receptors activate central vasopressinergic pathways to cause their cardiovascular effects.

Broad, LM et al., (2002). Eur. J. Pharmacol ., 452, 137-144
Moore, C et al. (2004) http://www.pa2online.org/Vol2Issue2abst017P.html

CM was supported by a BBSRC collaborative studentship. Y.W. present address is Central Research Institute of the Shanghai Pharmaceutical Group, Shanghai, China.