UNDIFFERENTIATED EFFECTS OF CALCIUM-ANTAGONISTS ON PRESSOR-RESPONSES TO SELECTIVE ALPHA-1 AND ALPHA-2 ADRENOCEPTOR AGONISTS IN ANESTHETIZED, SPINAL DOGS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 234  (3) , 728-734
Abstract
Whether pressor responses mediated by alpha-2 adrenoceptors are more susceptible to calcium antagonists than those mediated by alpha-1 adrenoceptors was investigated in anesthetized, spinal dogs. All drugs were administered i.v. Methoxamine (3-100 .mu./kg) or xylazine (3-300 .mu.g/kg) produced a sustained increase in mean arterial pressure but almost no effect on heart rate. Both the initial and the sustained phase of the pressor response to methoxamine were selectively antagonized by prazosin, whereas those to xylazine were selectively antagonized by yohimbine. These results indicate that the peripheral arterial bed of the dog comprises alpha-1 and alpha-2 adrenoceptors and that both the initial and sustained phases of the pressor response to methoxamine are predominantly mediated by alpha-1 adrenoceptors, whereas those to xylazine are mediated by alpha-2 adrenoceptors. The calcium antagonists, i.e., nifedipine (0.3-3 .mu.g/kg), diltiazem (10-100 .mu.g/kg) and KB-944 (10-100 .mu.g/kg), administered during the sustained phase of the pressor responses to equieffective doses of methoxamine (100 .mu.g/kg) and xylazine (1000 .mu.g/kg), lowered mean arterial pressure. The three calcium antagonists in these doses also lowered the base-line mean arterial pressure but to a lesser extent than the elevated one. These results although indicate that the calcium antagonists were more effective in lowering mean arterial pressure elevated by either an alpha-1 or alpha-2 adrenoceptor agonist than the base-line mean arterial pressure and that the sustained phase of the pressor response mediated by alpha-1 adrenoceptors would involve Ca++ influx as much as or more than those mediated by alpha-2 adrenoceptors.

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