In
urethane-anesthetized rabbits blood pressure was lowered by intraventricular
clonidine (30 microgram) and increased by intraventricular
methoxamine (1 mg).
Clonidine is well known to cause
hypotension by acting on central alpha-
adrenoceptors. The hypertensive effect of intraventricular
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 intraventricularly administered
clonidine and
methoxamine were examined in rabbits pretreated intraventricularly with various alpha-
adrenoceptor antagonists believed to exhibit preference for alpha 1- or alpha 2-adrenoceptors in the peripheral tissues. Pretreatment with 250 microgram of
yohimbine and with 500 microgram of
piperoxan inhibited the
clonidine hypotension, but pretreatment even with 2 mg of either of these drugs did not affect the
methoxamine hypertension. In contrast, pretreatment with 8 microgram of
prazosin inhibited the
methoxamine effect, whereas pretreatment even with 1 mg of
prazosin did not affect the
clonidine effect. Pretreatment with 8 microgram of
thymoxamine inhibited the
methoxamine effect, while it was necessary to increase the doses for each
drug up to 4 to 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 microgram 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, we 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.