Heimburger M, Davy M, Midol-Monnet M, Beslot F, Cohen Y
J Pharm Pharmacol. 1986 Sep;38(9):699-702. doi: 10.1111/j.2042-7158.1986.tb03115.x.
Chronic administration of acebutolol (15 mg kg-1 s.c. three times a week for five weeks, then 30 mg kg-1 for three weeks) did not lower blood pressure in 17 and 33 weeks-old spontaneously hypertensive rats (SHR). At the end of this treatment, the plasma concentrations of acebutolol and diacetolol were measured by HPLC. After 24 h, acebutolol was absent from plasma while diacetolol was lower after chronic treatment than after acute administration. Twenty-four hours after the last injection of acebutolol, both isoprenaline-induced tachycardia and vasodilatation were reduced. The vasomotor agents, noradrenaline, bradykinin and angiotensin, exhibited the same activity in control and treated SHR. These findings suggest that the lack of antihypertensive effect of acebutolol in SHR may be the result of a decrease in diacetolol formation together with blockade of beta 2 vascular receptors.
对17周龄和33周龄的自发性高血压大鼠（SHR）进行醋丁洛尔长期给药（15毫克/千克，皮下注射，每周三次，共五周，然后30毫克/千克，持续三周），并未降低其血压。在该治疗结束时，通过高效液相色谱法测定血浆中醋丁洛尔和双醋洛尔的浓度。24小时后，血浆中未检测到醋丁洛尔，而长期治疗后的双醋洛尔浓度低于急性给药后。最后一次注射醋丁洛尔24小时后，异丙肾上腺素诱导的心动过速和血管舒张均减弱。血管舒缩剂去甲肾上腺素、缓激肽和血管紧张素在对照和治疗的SHR中表现出相同的活性。这些发现表明，醋丁洛尔在SHR中缺乏降压作用可能是双醋洛尔生成减少以及β2血管受体被阻断的结果。
