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

Abstract

The purpose of this study was to evaluate the effects of the calcium channel blocker verapamil on CNS modulation of blood pressure and to determine whether its effects were mediated through central cholinergic muscarinic receptors. Unanesthetized and unrestrained Wistar rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received verapamil 50μg/kg, either into the lateral cerebral ventricle (ICV) or intravenously (i.v.). The role of central cholinergic muscarinic receptors was assessed by administration of atropine sulphate, 20μg/kg, ICV prior to verapamil. Verapamil ICV but not i.v. produced a significant (p<0.05) decrease in blood pressure and heart rate. Atropine sulphate, ICV, significantly (p<0.05) increased heart rate but did not alter blood pressure. This dose of atropine antagonized the effect of acetylcholine as it significantly (p<0.05) altered the effects of the cholinesterase inhibitor physostigmine on blood pressure and heart rate. Atropine sulfate did not significantly alter the blood pressure response to verapamil. Verapamil-induced reduction in heart rate completely overcame the increase in heart rate produced by atropine and the heart rate was decreased to the same extent after verapamil regardless of atropine pretreatment. These data suggest that the brain is a site of action of the blood pressure reduction produced by the calcium channel antagonist verapamil. The action on blood pressure and heart rate can be independent of mechanisms operating through central cholinergic muscarinic receptors.(Hypertens Res 1993; 16: 97-103)