Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: comparison of systemic vs. local effects.
Calcium entry blockade in vivo preferentially antagonizes systemic pressor responses to alpha-2 adrenergic agonists, whereas relatively sparing alpha-1 mediated vasoconstriction; however, in vitro studies have given results discordant from those obtained in vivo. Because of these discrepancies we have compared the effect of calcium entry blockade by nitrendipine on systemic and local (autoperfused hindquarters) pressor responses to selective adrenergic agonists: cirazoline for alpha-1 and B-HT 920 for alpha-2. Pithed, vagotomized, normotensive Sprague-Dawley rats were used. Confirming previous results, nitrendipine (3.0 and 30.0 micrograms/kg/min X 15 min) selectively antagonized the systemic pressor responses to B-HT 920 without affecting significant responses to the alpha-1 agonist. However, in the isolated, autoperfused hindquarters of pithed rats, these same doses of nitrendipine depressed by 36 and 45% the maximum vasoconstrictor response to cirazoline. Because no significant vasoconstrictor response to B-HT 920 could be demonstrated in this same preparation, we induced supersensitivity to the alpha-2 agonist by reserpine pretreatment (0.3 mg/kg X 3 days). Reserpine increased vascular responsiveness to B-HT 920, without modifying its selective alpha-2 agonistic properties, as assessed by the use of selective alpha-1 (prazosin, 0.5 mg/kg i.v.) and alpha-2 (rauwolscine, 0.5 mg/kg i.v.) antagonists and of phentolamine (5 mg/kg i.v.), a nonspecific alpha adrenergic antagonist. After pretreatment with reserpine, nitrendipine antagonized both the B-HT 920-mediated vasoconstriction (by an average of 40 and 57%, respectively) and the cirazoline alpha-1-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Pedrinelli
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Tarazi
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D002121:Calcium Channel Blockers; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C024763:talipexole; D012110:Reserpine; D009568:Nitrendipine; D009543:Nifedipine; C014282:cirazoline