Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, C4



Moore,Christopher ; Wang,Yun ; Ramage,Andrew G;

1. Pharmacology, University College London, London, United Kingdom. 2. Lilly Research Centre, Eli Lilly Company, Windlsham, Surrey, United Kingdom. 3. Pharmacology, University College London, London, United Kingdom.

Activation of central α4β2 and α7 nACh receptors with TC−2559 and Astra IV, respectively, causes a rise in mean arterial blood pressure (MAP), sympathoexcitation, but no change in heart rate (HR) in anaesthetized rats (Moore et al. 2004). However, nicotine i.c.v. although causing a rise in MAP, causes sympathoinhibition. Nicotine i.c.v. has been shown to cause a rise in MAP associated with the release of vasopressin (Iitake et al. 1986). This release of vasopressin would explain the sympathoinhibition, as it would cause a peripherally mediated rise in BP which would activate the baroreceptor reflex. Experiments were carried out to examine the effects of these agonists, in the presence (I.V.) of a V1 receptor antagonist, on the above cardiovascular variables. 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 saline (5 μl; i.c.v.) in the presence of the V1 receptor antagonist 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. In presence of V1 receptor antagonist ([β-Mercapto-β,β-cyclopentamethylenepropionyl1,O-Me-Tyr2,Arg8]-Vasopressin; 30 μg kg-1, I.V.), cardiovascular effects of nicotine (0.3 μmol kg-1; i.c.v.; n=5) were now completely blocked. TC-2559 (3 μmol kg-1; i.c.v.; n=5) also now caused no significant change in MAP and HR but RNA still significantly increased (30 ± 6% at 3 min) but compared to TC−2559 alone it was significantly decreased. The effects of Astra IV (3 μmol kg-1; i.c.v.; n=5) on MAP were also blocked along with the sympathoexcitation. This study confirms that i.c.v. nicotine causes a rise in MAP due to vasopressin release and is consistent with the view that the renal sympathoinhibition is secondary to this rise. The data indicate that vasopressin release can be caused by either α4β2 and α7 nACh receptor activation. Interestingly, the renal sympathoexcitation caused by the nACh receptor agonists is also mediated by V1 receptors.

Where applicable, experiments conform with Society ethical requirements