Calcium channels mediate angiotensin II-induced drinking behaviour and c-fos expression in the brain

Abstract

It is widely accepted that calcium ions are critically important in both short- and/or long-lasting responses of neurons to a stimulus. We have shown previously that NMDA receptors play a role in dipsogenic responses and c-fos expression induced by intracerebroventricular (i.c.v.) infusion of angiotensin II (Ang II). Since NMDA receptors are known to be linked to receptor-operated calcium channels, this study determined whether voltage dependent calcium channels are also involved in Ang II-induced behavioural (drinking) and endocrine responses as well as c-fos expression. The antidipsogenic actions of three L-type calcium channel antagonists, nifedipine, diltiazem and verapamil on Ang II-induced drinking behaviour were studied. These bind to the dihydropyridine, phenylalkylamine and benzothiazepine sites respectively. Rats (Lister-hooded) pre-treated i.c.v. with either 25 or 100 microg nifedipine, followed by 25 pmol Ang II, drank significantly less water than controls during the first 15 min after infusion. However, rats pre-treated with i.c.v. 100 microg diltiazem or verapamil showed no change in Ang II-induced drinking behaviour. The antidipsogenic actions of N- and P-type calcium channel antagonists omega-conotoxin GVIA and omega-conotoxin MVIIC were also evaluated. Rats pre-treated with 5 pmol or 20 pmol omega-conotoxin GVIA did show a slight but not significant suppression of water intake, particularly after the higher dose. Rats pre-treated with omega-conotoxin MVIIC drank almost the same amount of water as those pre-treated with saline. Nifedipine was found to suppress both Ang II-induced corticosterone release and c-fos expression in the following areas: organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MNPO), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The results described in this paper provide evidence that calcium channels play important roles in the Ang II-induced behavioural and endocrine responses, and in the expression of the immediate-early gene c-fos. This suggests that an L-type calcium channel may participate both short- and longer-term neuronal actions of Ang II.