Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: comparison with noncalcium entry blocker vasodilators in absence and presence of phenoxybenzamine pretreatment.
To investigate the in vivo interaction between calcium entry blockade by nitrendipine (a dihydropyridine calcium entry blocker) and alpha adrenergic-mediated end-organ responsiveness, four series of experiments were carried out in normal Sprague-Dawley rats. In ganglion-blocked rats (hexamethonium, 10 mg/kg i.p. plus atropine, 1.0 mg/kg i.p.), nitrendipine (0.3 mg/kg) antagonized the pressor responses to angiotensin II and vasopressin as well as to norepinephrine, thus indicating the lack of specificity of its antagonism to alpha adrenergic vasoconstriction. The results of the next two series of experiments showed first that, in pithed rats, nitrendipine (0.01 to 0.3 mg/kg) in presence of prazosin shifted the norepinephrine pressor dose-response curves to the right whereas it was ineffective in yohimbine-pretreated animals. These data, suggesting a preferential alpha-2 antagonism by nitrendipine, were confirmed further by its little effect on pressor responses to methoxamine as contrasted with its marked progressive depression of the maximum response to B-HT 920 (about 80% at the highest rate of infusion). However, qualitatively similar results were obtained by the noncalcium entry blocker vasodilators, both sodium nitroprusside and hydralazine, both of which led to minor shifts to the right of the methoxamine pressor dose-response curves, whereas dose-dependently depressing the maximum pressor response to B-HT 920 (about 70 and 40%, respectively). Thus, calcium entry blockade appeared to antagonize preferentially alpha-2-mediated vasoconstriction, but this effect was common to other vasodilators devoid of calcium entry blocking properties.(ABSTRACT TRUNCATED AT 250 WORDS)
Pedrinelli
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Tarazi
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D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006830:Hydralazine / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D009599:Nitroprusside / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001381:Azepines; D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; D010643:Phenoxybenzamine; D009599:Nitroprusside; D006830:Hydralazine; C024763:talipexole; D009568:Nitrendipine; D008729:Methoxamine; D009543:Nifedipine