Calcium channel blockade attenuates angiotensin II-induced drinking in rats.
Lateral ventricular administration of angiotensin II (ANG II) 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)-1-4-dihydro-2,6-dimethyl-3,5-pyridine-dic arb oxylic 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 micrograms/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 micrograms) attenuated ANG II-induced drinking to 62 and 22% of control, respectively. Results with the 30-micrograms dose were not different from the 3.0 dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcagnetti
D J
DJ
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095.
Schechter
M D
MD
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D017275:Isradipine; D004121:Dimethyl Sulfoxide