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DILTIAZEM AND VERAPAMIL LOWER BLOOD PRESSURE IN THE UNANAESTHETIZED RAT THROUGH CNS MECHANISMS INVOLVING ENDOGENOUS OPIOIDS
Author(s) -
Rabkin Simon W.
Publication year - 1991
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1991.tb01475.x
Subject(s) - diltiazem , verapamil , blood pressure , (+) naloxone , endogenous opioid , medicine , calcium , heart rate , calcium channel , antagonist , endocrinology , pharmacology , anesthesia , opioid , receptor
SUMMARY 1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intra‐cerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 μg/kg, or their diluent. 2. Diltiazem, at both 10 and 50 μg/kg i.c.v., produced significant ( P <0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 μg/kg but not at 10 μg/kg i.c.v., produced a significant ( P <0.05) decrease in blood pressure, while both doses significantly ( P <0.05) decreased heart rate. 3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 μg/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone. 4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pressure.