Pharmacological analysis of the actions of calcium entry blockers, felodipine, nifedipine and verapamil : interactions with pre- and postjunctional alpha adrenoceptors

The objective of the present study was to investigate the role of the autonomic nervous system in the hypotensive actions of the calcium entry blockers, felodipine, nifedipine and verapamil. Experiments were designed to determine the effects of these compounds on vascular sympathetic neuroeffector function under both in vivo and in vitro conditions. Intravenous administration of cumulative doses of felodipine in intact urethane anesthetized rats produced a sustained and significant decrease in arterial pressure up to 60 minutes in duration at the highest dose (0.8 [micromol]/kg) tested. Higher doses of nifedipine (0.9 [micromol]/kg) and verapamil (0.9 [micromol]/kg) produced transient but significant decreases in mean blood pressure which lasted for 10 minutes. When cardiac compensation was prevented by either bilateral vagotomy plus atropine (1 mg/kg) or propranolol (1 mg/kg) alone or bilateral vagotomy together with atropine plus propranolol, nifedipine and verapamil were also able to reduce arterial pressure. However after ganglionic blockade (chlorisondamine plus atropine) only felodipine was effective in lowering arterial blood pressure. In pithed rat preparations felodipine (0.5 [micromol]/kg), nifedipine (1.2 [micromol]/kg) and verapamil (0.9 [micromol]/kg) significantly attenuated pressor responses to spinal sympathetic stimulation and exogenous norepinephrine. While all three agents attenuated blood pressure responses to norepinephrine as well as spinal stimulation, felodipine appeared to be more effective in reducing pressor responses to intravenous norepinephrine than those of spinal stimulation. [...]