Timmermans P B, de Jonge A, van Meel J C, Mathy M J, van Zwieten P A
J Cardiovasc Pharmacol. 1983 Jan-Feb;5(1):1-11. doi: 10.1097/00005344-198301000-00001.
The pressor effects of intravenous B-HT 920 in pithed cats were sensitive to antagonism by yohimbine (1 mg/kg i.v.), but not by prazosin (1 mg/kg i.v.). In contrast, prazosin profoundly affected the vasoconstriction caused by intravenous (-)-phenylephrine, whereas yohimbine only slightly influenced this response. These results confirm and extend earlier observations which favor a distinct subclassification of vascular postsynaptic alpha-adrenoceptors into alpha 1- and alpha 2-subtypes. Vasoconstriction in pithed cats by B-HT 920 was markedly antagonized by low doses (30 and 100 micrograms/kg) of nifedipine in a noncompetitive manner. The hypertensive responses to (-)-phenylephrine were moderately attenuated in a competitive fashion. These findings are consistent with the concept that extracellular calcium ions are indispensable for linking vascular alpha 2-adrenoceptor activation to vasoconstriction in vivo. Nifedipine (up to 1 mg/kg i.v.) neither interfered with the tachycardia induced by electrical stimulation in pithed normotensive rats nor influenced the inhibitory effect of B-HT 920. Clonidine's (0.3 mg/kg i.p.) prolongation of the hexobarbitone-induced loss of the righting reflex in mice was unchanged after nifedipine administration (up to 1 mg/kg i.p.). The central hypotensive action of clonidine in anesthetized cats (1 microgram/kg via vertebral artery) and in anesthetized normotensive rats (3-30 micrograms/kg i.c.v.) was reduced by nifedipine (30 and 100 micrograms/kg i.v. or i.c.v.). The results show a differential influence of nifedipine on functional responses in vivo caused by stimulation of pre- and postsynaptic alpha 2-adrenoceptors. In contrast to its inability to inhibit alpha 2-adrenoceptor-mediated effects at presynaptic sites, this calcium entry blocker impairs postsynaptic alpha 2-adrenoceptor-induced responses.
静脉注射B-HT 920对脊髓毁损猫的升压作用对育亨宾（静脉注射1 mg/kg）的拮抗敏感，但对哌唑嗪（静脉注射1 mg/kg）不敏感。相反，哌唑嗪能显著影响静脉注射（-）-去氧肾上腺素引起的血管收缩，而育亨宾仅轻微影响该反应。这些结果证实并扩展了早期的观察结果，支持将血管突触后α-肾上腺素能受体明确细分为α1和α2亚型。低剂量（30和100微克/千克）的硝苯地平以非竞争性方式显著拮抗脊髓毁损猫中B-HT 920引起的血管收缩。对（-）-去氧肾上腺素的高血压反应以竞争性方式适度减弱。这些发现与细胞外钙离子对于在体内将血管α2-肾上腺素能受体激活与血管收缩联系起来不可或缺的概念一致。硝苯地平（静脉注射高达1 mg/kg）既不干扰脊髓毁损正常血压大鼠电刺激诱导的心动过速，也不影响B-HT 920的抑制作用。给予硝苯地平（腹腔注射高达1 mg/kg）后，可乐定（腹腔注射0.3 mg/kg）延长小鼠六巴比妥诱导的翻正反射消失的作用未改变。硝苯地平（静脉注射或脑室内注射30和100微克/千克）降低了可乐定在麻醉猫（通过椎动脉1微克/千克）和麻醉正常血压大鼠（脑室内注射3 - 30微克/千克）中的中枢降压作用。结果显示硝苯地平对体内由突触前和突触后α2-肾上腺素能受体刺激引起的功能反应有不同影响。与其无法抑制突触前部位α2-肾上腺素能受体介导的效应相反，这种钙通道阻滞剂损害突触后α2-肾上腺素能受体诱导的反应。
