EFFECTS OF A-ADRENOCEPTOR ANTAGONISTS ADMINISTERED INTRAVENTRICULARLY ON CENTRAL HYPOTENSIVE ACTION OF CLONIDINE AND ON CENTRAL HYPERTENSIVE ACTION OF METHOXAMINE IN RABBITS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 257  (1) , 66-76
Abstract
In urethane-anesthetized rabbits blood pressure was lowered by intraventricular [i.v.c.] clonidine (30 .mu.g) and increased by i.v.c. methoxamine (1 mg). Clonidine causes hypotension by acting on central .alpha.-adrenoceptors. The hypertensive effect of i.v.c. methoxamine was not observed in cord-sectioned rabbits, in guanethidine-treated adrenalectomized rabbits and in phentolamine-treated rabbits, indicating the effect was central in origin. These responses to i.v.c. administered clonidine and methoxamine were examined in rabbits pretreated i.v.c. with various .alpha.-adrenoceptor antagonists believed to exhibit preference for .alpha.1- or .alpha.2-adrenoceptors in the peripheral tissues. Pretreatment with 250 .mu.g of yohimbine and with 500 .mu.g of piperoxan inhibited the clonidine hypotension, but pretreatment even with 2 mg of either of these drugs did not affect the methoxamine hypertension. Pretreatment with 8 .mu.g of prazosin inhibited the methoxamine effect, while pretreatment even with 1 mg of prazosin did not affect the clonidine effect. Pretreatment with 8 .mu.g of thymoxamine inhibited the methoxamine effect, while it was necessary to increase the doses for each drug up to 4-8 times to oppose the clonidine effect. Pretreatment with 2 mg of labetalol inhibited the methoxamine effect but was ineffective against clonidine. Pretreatment with 500 .mu.g of phentolamine was effective in antagonizing the clonidine effect, but twice the dose was needed to inhibit the methoxamine effect. From the findings that the hypertensive effect of methoxamine and the hypotensive effect of clonidine were inhibited differently by various .alpha.-adrenoceptor antagonists and that the selectivity of these antagonists for the methoxamine and clonidine effect is similar, respectively, to that for .alpha.1- and .alpha.2-adrenoceptors in the peripheral tissues, it was concluded that the methoxamine hypertension and the clonidine hypotension are due to the stimulation of .alpha.1- and .alpha.2-adrenoceptors in the brain, respectively.