Sinha J N, Sharma D K, Gurtu S, Pant K K, Bhargava K P
Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(3):193-7. doi: 10.1007/BF00505317.
Microinjection of noradrenaline or phenylephrine into the nucleus locus coeruleus of cats induced a dose dependent and long lasting hypotension. Clonidine was required in a dose of 1 microgram for eliciting a significant hypotension while its lower doses (up to 500 ng) failed to elicit any significant cardiovascular alteration. The effects on heart rate evoked by these agents were insignificant. Microinjection of alpha-adrenoceptor antagonists prazosin, piperoxan and RX 781094 per se did not evoke any significant cardiovascular effects and only prazosin pretreatment showed dose dependent antagonism of the hypotensive effect of clonidine. Piperoxan was required in four times higher dose (20 micrograms) to partially antagonize the clonidine induced hypotension. RX 781094, a selective alpha 2-adrenoceptor antagonist, however, even up to a dose of 20 micrograms (four times that of prazosin) did not alter the effect of clonidine. Similar pattern of antagonism was also seen for noradrenaline and phenylephrine. The results demonstrate the presence of alpha 1-adrenoceptors in the nucleus locus coeruleus, the activation of which leads to a fall in blood pressure.
向猫的蓝斑核微量注射去甲肾上腺素或苯肾上腺素可引起剂量依赖性和持久性低血压。可乐定需要1微克的剂量才能引起显著的低血压,而其较低剂量(高达500纳克)未能引起任何显著的心血管改变。这些药物对心率的影响不显著。微量注射α-肾上腺素能受体拮抗剂哌唑嗪、哌罗克生和RX 781094本身不会引起任何显著的心血管效应,只有哌唑嗪预处理显示出对可乐定降压作用的剂量依赖性拮抗作用。哌罗克生需要四倍高的剂量(20微克)才能部分拮抗可乐定引起的低血压。然而,选择性α2-肾上腺素能受体拮抗剂RX 781094,即使高达20微克的剂量(哌唑嗪剂量的四倍)也不会改变可乐定的作用。去甲肾上腺素和苯肾上腺素也观察到类似的拮抗模式。结果表明蓝斑核中存在α1-肾上腺素能受体,其激活导致血压下降。