CALCIUM ENTRY BLOCKADE BY NITRENDIPINE AND ALPHA-ADRENERGIC RESPONSIVENESS INVIVO - COMPARISON OF SYSTEMIC VS LOCAL-EFFECTS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (3) , 643-649
Abstract
Ca 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 the effect was compared of Ca 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 .mu.g/kg per min .times. 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 vasconstrictor response to B-HT 920 could be demonstrated in this same preparation, supersensitivity to the .alpha.-2 agonist was induced by reserpine pretreatment (0.3 mg/kg .times. 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 vasconstriction. Thus, in contrast with systemic pressor responses, no evidence for selective interference with .alpha.-2 agonists by Ca entry blockers selectivity could be demonstrated in isolated rat hindquarters perfused at constant flow; both .alpha.-1 and .alpha.-2 adrenergic-mediated vasoconstriction in that vascular bed were equally sensitive to Ca entry blockade.

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