Calcium channel blockade attenuates angiotensin II-Induced drinking in rats

Abstract

Lateral ventricular administration of angiotensin II (ANGII) produces potent dipsogenic effects in water-sated rats. ANG II seems to require functional voltage-gated calcium channels on neurons throughout circumventricular brain sites to exert its effects. Although there are at least three types of calcium channels, only L-type calcium channel-blocking drugs have been reported to decrease drinking. (4-(4-Benzofurazanyl)-l-4-dihydro-2,6-dimethyl-3,5-pyridine-dicarboxylic acid methyl 1-methyl-ethyl ester) [PN 200-110; isradipine (ISR)], a selective L-type calcium channel blocker, has been shown to attenuate significantly the intake of sweetened water in water-sated rats following either peripheral or ICV administration, but ISR does not affect plain-water intake in water-deprived rats. The present experiment was designed to determine whether ISR would attenuate ANG II-induced drinking that is not either motivated by palatability or dependent on deprivation. Rats, each fitted with chronic indwelling ventricular cannulae, were pretreated with ISR (0.3, 3.0, and 30 μg/rat; ICV). ANG II (40 ng/rat; ICV) was administered 10 min later and rats were allowed free access to water for 15 min. Injections of ANG II plus saline and ANG II plus the ISR vehicle (dimethyl sulfoxide) did not attenuate ANG II-induced polydipsia, whereas ANG II+ISR (0.3 and 3.0 μg) attenuated ANG II-induced drinking to 62 and 22% of control, respectively. Results with the 30-μg dose were not different from the 3.0 dose. In conclusion, our findings support the hypothesis that ANG II-induced polydipsia is mediated, at least in part, by calcium voltage-dependent channels as the pretreatment with ISR effectively blocked ANG II-induced drinking.