Buckingham R E, Hamilton T C, Robson D
Br J Pharmacol. 1977 Jul;60(3):461-9. doi: 10.1111/j.1476-5381.1977.tb07523.x.
1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors.
1 描述了口服吲哚洛尔对清醒正常血压大鼠和醋酸脱氧皮质酮（DOCA）/盐水高血压大鼠（DS大鼠）的降压反应。在DS大鼠中，吲哚洛尔（10 - 50微克/千克）可使血压呈剂量依赖性下降，并使静息心率升高。
2 普萘洛尔（5毫克/千克）可预防DS大鼠口服吲哚洛尔（50微克/千克）所产生的降压反应和心动过速，提示吲哚洛尔的作用是通过β - 肾上腺素能受体刺激介导的。
3 美加明（10毫克/千克）给药后，DS大鼠口服吲哚洛尔（50微克/千克）可使血压进一步下降，提示其降压作用可能在外周血管系统中介导。
4 口服吲哚洛尔（10或50微克/千克）预处理可使脊髓横断DS大鼠的神经源性心动过速减轻；吲哚洛尔（50微克/千克，口服）也可拮抗神经源性升压作用。
5 口服或腹腔注射50微克/千克吲哚洛尔可使DS大鼠产生明显且逐渐增强的快速起效（20分钟）的降压反应，而相同剂量静脉注射则产生较小的延迟起效（80分钟）的反应。
6 在麻醉的DS大鼠中，口服50微克/千克吲哚洛尔（提前2小时）或静脉注射（提前1小时）预处理可产生同等程度的心脏β - 肾上腺素能受体阻滞。
7 对清醒的DS大鼠静脉注射2毫克/千克吲哚洛尔后，在研究的前60分钟内，静脉注射3微克/千克异丙肾上腺素所产生的心动过速几乎被消除，而对吲哚洛尔的降压反应起效延迟（100分钟）。
8 用80毫克/千克丙胺苯丙酮（SKF 525 - A）预处理抑制代谢酶活性可预防DS大鼠口服50微克/千克吲哚洛尔所产生的降压反应和心动过速。
9 结果提示，吲哚洛尔对清醒DS大鼠血压和心率的作用是由一种通过刺激外周β - 肾上腺素能受体起作用的代谢产物介导的。
