1987 Volume 151 Issue 1 Pages 65-80
IMAI, Y., ABE, K., SASAKI, S., MINAMI, N., SEINO, M., YOSHINAGA, K. and TAIRA, N. The Mechanism of Centrally Mediated Cardiovascular Actions of the Three Structurally Different Calcium Antagonists, Verapamil, Diltiazem and Nicardipine, in Rats. Tohoku J. exp. Med., 1987, 151(1), 65-80-Centrally mediated cardiovascular effects of the three structurally different calcium antagonists (Ca-antagonists), i.e., verapamil, diltiazem and nicardipine, were studied in rats. In conscious rats, when administered intracerebroventricularly (i.c.v.) in doses of 0.3, 1 and 3μg/kg/min for 30min, all the three Ca-antagonists induced dose-dependent increases in mean arterial pressure (MAP) and pulse rate (PR), whereas nicardipine administered intravenously (i.v.) caused a decrease in MAP and an increase in PR. In anesthetized rats all the three Ca-antagonists in a dose of 3μg/kg/min for 60min i.c.v, significantly potentiated the hypotensive and bradycardic effects of i.c.v. clonidine. Nicardipine, in a dose of 0.3μg/kg/min for 60min i.c.v., attenuated the hypotensive and bradycardic effects of i.c.v clonidine or B-HT 920, an α2-adrenoceptor agonist, in anesthetized rats, whereas it did not modify the cardiovascular effect of i.c.v. angiotensin II or γ-aminobutylic acid in conscious rats. Nicardipine, in a dose of 0.3μg/kg/min for 60min i.v., did not modulate the hypotensive and bradycardic effects of i.c.v. clonidine. 3-Isobutyl-1-methylxanthine (IBMX), a cyclic AMP phosphodiesterase inhibitor, in a dose of 3 μg/kg/min for 60min i.c.v., also attenuated the hypotensive and bradycardic effects of i.c.v. clonidine. Potentiation by the three i.c.v. Ca-antagonists of the hypotensive and bradycardic effects of clonidine would be explainable if their inhibitory effect on Ca-influx is exerted at presynaptic nerve terminals but not at postsynaptic. The mechanisms of the cardiovascular effect of i.c.v. Ca-antagonists still remain to be elucidated but may be independent of a central α2-adrenoceptor mechanism. Dihydropyridine Ca-antagonists like nicardipine are also potent inhibitor of cyclic AMP phosphodiesterase. Since IBMX mimicked the effect of nicardipine, the effect of a low dose of i.c.v. nicardipine in attenuating the hypotensive and bradycardic effects of i.c.v. clonidine may be mediated by inhibition of cyclic AMP phosphodiesterase in the central nervous system.
