The mechanism of centrally mediated cardiovascular actions of the three structurally different calcium antagonists, verapamil, diltiazem and nicardipine, in rats.

Abstract

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 (icy. ) in doses of 0.3, 1 and 3,ug/kg/min for 30 min, all the three Ca-antagonists induced dose-dependent increases in mean arterial pressure (MAP) and pulse rate (PR), whereas nicardipine administered intravenously (iv.) caused a decrease in MAP and an increase in PR. In anesthetized rats all the three Ca-antagonists in a dose of 3 ,u g/kg/min for 60 min i.c.v, significantly potentiated the hypotensive and bradycardic effects of icy. clonidine. Nicardipine, in a dose of 0.3 1cg/kg/min for 60 min icy., attenuated the hypotensive and bradycardic effects of icy. clonidine or B-HT 920, an a2-adrenoceptor agonist, in anesthetized rats, whereas it did not modify the cardiovascular effect of icy. angiotensin II or y-aminobutylic acid in conscious rats. Nicardipine, in a dose of 0.3 1ug/kg/min for 60 mm iv., did not modulate the hypotensive and bradycardic effects of icy. clonidine. 3-Isobutyl-lmethylxanthine (IBMX), a cyclic AMP phosphodiesterase inhibitor, in a dose of 3 ,ug/kg/min for 60 min icy., also attenuated the hypotensive and bradycardic effects of icy. clonidine. Potentiation by the three icy. 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 icy. Ca-antagonists still remain to be elucidated but may be independent of a central a2-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 icy. nicardipine in attenuating the hypotensive and bradycardic effects of icy. clonidine may be mediated by inhibition of cyclic AMP phosphodiesterase in the central nervous system. clonidine ; IBMX ; central nervous system ; blood pressure ; pulse rate

Verapamil in the Brain Lowers Blood Pressure and Heart Rate Independent of Central Muscarinic Receptors.

“…However, there are several other reasons that conceptually support the findings of the present study rather than those of Monostastue et al (33). Their observations on the increase in blood pressure and heart rate with this dihydropyridine calcium antagonist are difficult to reconcile with the reduction in blood pressure produced by calcium antagonists (9, 13,14,17). Second, calcium channel agonists increase blood pressure after their intracerebral administration (9,31).…”