Calcium entry blockade and alpha-adrenergic responsiveness in vivo.
In an initial series of studies in pithed normotensive rats, nitrendipine (3, 10, 30 micrograms/kg/min X 15 min) preferentially antagonized the pressor responses to BHT 920, a selective alpha 2-adrenergic agonist, while hardly interfering with responses to methoxamine, a selective alpha 1-agonist. The preferential alpha 2-antagonism by nitrendipine (0.01-0.3 mg/kg i.v.) was also shown by its greater antagonism of pressor responses to norepinephrine in propranolol (1 mg/kg)-prazosin (0.3 mg/kg i.v.)-pretreated pithed rats (alpha 1-receptors blocked, alpha 2 exposed) than in propranolol-yohimbine (0.3 mg/kg)-pretreated preparations (alpha 2 blocked, alpha 1 exposed). However, the effect of nitrendipine on vascular alpha 2-adrenergic responsiveness was found to be not specific for calcium entry blockers (CaEB) since vasodilators without calcium entry blocking properties [sodium nitroprusside (3-30 mg/kg/min X 15 min) and hydralazine (0.03-3.0 mg/kg/min X 15)], gave the same pattern of interference with pressor responses to methoxamine and BHT 920 in exactly the same model. Both vasodilators depressed the pressor dose-response curves to BHT 920, while sparing those to methoxamine. Thus, calcium entry blockade preferentially antagonized alpha 2-mediated vasoconstriction, but this effect was common to other non-CaEB vasodilators. The reason for the relative sparing by CaEB of pressor responses to alpha 1-adrenergic stimulation was sought in a second series of studies of dose-response curves to methoxamine following partial alpha-adrenoceptor inactivation by phenoxybenzamine (0.3 mg/kg i.v.). In these conditions, nitrendipine (30 micrograms/kg/min), sodium nitroprusside (30 micrograms/kg/min), and hydralazine (3 mg/kg/min) all strongly depressed the pressor responses to methoxamine.(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*; D006830:Hydralazine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D001381:Azepines; D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D009599:Nitroprusside; D006830:Hydralazine; C024763:talipexole; D009568:Nitrendipine; D009543:Nifedipine