Kawasaki H, Takasaki K
Department of Pharmacology, Miyazaki Medical College, Japan.
Arch Int Pharmacodyn Ther. 1987 Oct;289(2):217-33.
The hypertensive response mediated by central alpha 2-adrenoceptor stimulation was investigated in freely moving, normotensive rats with chronic arterial catheters and guide cannulas. The alpha 1-adrenoceptor agonists (methoxamine, phenylephrine, ST 587) and the alpha 2-adrenoceptor agonists (B-HT 920, clonidine, oxymetazoline) injected intravenously (i.v.) caused a rise in mean blood pressure. The rank order of potency of the agonists to produce 25 mm Hg of pressor response (the effective dose; ED25) was oxymetazoline (0.64 microgram/kg) greater than phenylephrine (1.05 microgram/kg) greater than clonidine (1.6 microgram/kg) greater than ST 587 (5.4 micrograms/kg) greater than B-HT 920 (19.0 micrograms/kg) greater than methoxamine (19.5 micrograms/kg). The intracerebroventricular (i.c.v.) injection of alpha 2-adrenoceptor agonists, B-HT 920 (3 to 300 micrograms/kg), clonidine (3 to 100 micrograms/kg) and oxymetazoline (3 to 100 micrograms/kg) produced a dose-dependent and long-lasting pressor response associated with bradycardia, without showing a significant depressor response for up to 90 min at any of the doses used. The i.c.v. injection of alpha 1-adrenoceptor agonists, methoxamine (100 to 500 micrograms/kg), phenylephrine (100 to 500 micrograms/kg) and ST 587 (100 to 300 micrograms/kg) produced a short-lasting pressor response with variable changes in heart rate. In addition, a significant long-lasting depressor response concomitant with a decrease in heart rate was observed 30-60 min after the injection at higher doses. Dose-response curves for pressor responses to alpha 2-adrenoceptor agonists were located to the left of those for alpha 1-adrenoceptor agonists. The rank order of potency of the agonists injected i.c.v. in producing pressor responses with ED25 was clonidine (12.0 micrograms/kg) greater than oxymetazoline (14.0 micrograms/kg) greater than B-HT 920 (16.0 micrograms/kg) much greater than ST 587 (125 micrograms/kg) greater than phenylephrine (235 micrograms/kg) greater than methoxamine (310 micrograms/kg). Central (i.c.v.) pretreatment with yohimbine (100 micrograms/kg) abolished hypertensive responses to centrally administered alpha 2-adrenoceptor agonists but the treatment with prazosin (30 micrograms/kg) was less effective in inhibiting the hypertensive responses. In pentobarbital-anesthetized rats, pressor responses to i.c.v. injection of alpha 1- and alpha 2-adrenoceptor agonists were significantly inhibited and a long-lasting depressor response was induced by alpha 2-adrenoceptor agonists, whereas depressor responses to alpha 1-adrenoceptor agonists were not affected.(ABSTRACT TRUNCATED AT 400 WORDS)
在具有慢性动脉导管和引导套管的自由活动的正常血压大鼠中，研究了由中枢α2-肾上腺素能受体刺激介导的高血压反应。静脉注射（i.v.）α1-肾上腺素能受体激动剂（甲氧明、去氧肾上腺素、ST 587）和α2-肾上腺素能受体激动剂（B-HT 920、可乐定、羟甲唑啉）可导致平均血压升高。产生25 mmHg升压反应（有效剂量；ED25）的激动剂效力顺序为：羟甲唑啉（0.64微克/千克）＞去氧肾上腺素（1.05微克/千克）＞可乐定（1.6微克/千克）＞ST 587（5.4微克/千克）＞B-HT 920（19.0微克/千克）＞甲氧明（19.5微克/千克）。脑室内（i.c.v.）注射α2-肾上腺素能受体激动剂B-HT 920（3至300微克/千克）、可乐定（3至100微克/千克）和羟甲唑啉（3至100微克/千克）产生剂量依赖性和持久的升压反应，并伴有心动过缓，在所使用的任何剂量下，长达90分钟均未显示出明显的降压反应。脑室内注射α1-肾上腺素能受体激动剂甲氧明（100至500微克/千克）、去氧肾上腺素（100至500微克/千克）和ST 587（100至300微克/千克）产生短暂的升压反应，心率有不同变化。此外，在较高剂量注射后30 - 60分钟观察到明显的持久降压反应，同时心率下降。α2-肾上腺素能受体激动剂升压反应的剂量反应曲线位于α1-肾上腺素能受体激动剂的左侧。脑室内注射激动剂产生ED25升压反应的效力顺序为：可乐定（12.0微克/千克）＞羟甲唑啉（14.0微克/千克）＞B-HT 920（16.0微克/千克）＞＞ST 587（125微克/千克）＞去氧肾上腺素（235微克/千克）＞甲氧明（310微克/千克）。用育亨宾（100微克/千克）进行中枢（i.c.v.）预处理可消除对中枢给予的α2-肾上腺素能受体激动剂的高血压反应，但用哌唑嗪（30微克/千克）治疗在抑制高血压反应方面效果较差。在戊巴比妥麻醉的大鼠中，对脑室内注射α1-和α2-肾上腺素能受体激动剂的升压反应被显著抑制，α2-肾上腺素能受体激动剂诱导出持久的降压反应，而对α1-肾上腺素能受体激动剂的降压反应未受影响。（摘要截断于400字）
