Forster C, Campbell P M
Division of Cardiology, University of Toronto, St Michael's Hospital, Ontario, Canada.
Eur J Pharmacol. 1993 Sep 28;242(2):119-28. doi: 10.1016/0014-2999(93)90071-o.
The effects of nifedipine (10(-8) and 10(-7) M) on alpha-adrenergic responses of the dorsal pedal artery and saphenous vein were examined from dogs with pacing-induced heart failure. Two groups of dogs had their right ventricles paced at 250 beats/min: group (1) 1 week of pacing (mild heart failure) and group (2) paced for a mean period of 25.8 days (peak heart failure). Nifedipine non-competitively antagonised 6-allyl-2-amino-5,6,7,8-tetrahydro-4H- thiazolo[4,5-d]azepin dihydrochloride (BHT 920)-induced contractions to the same extent (i.e. at control, mild heart failure and peak heart failure) and IC50 values were as follows: for dorsal pedal artery 3.9 (1.8-6.1) nM, 4.4 (1.2-8.4) nM and 8.5 (2.9-38.9) nM, respectively; for saphenous vein 13.0 (4.6-26.0) nM, 13.0 (7.3-18.6) nM and 19.0 (9.3-32.8) nM, respectively). Before the onset of pacing, nifedipine did not affect concentration-effect curves generated to noradrenaline or phenylephrine in either the artery or the vein. After 1 week of pacing, nifedipine (10(-7) M) inhibited contractions to noradrenaline in the artery and the vein (70 +/- 5% for the artery and 51 +/- 4% for the vein). Nifedipine had no effect on phenylephrine-induced contractions. At peak heart failure, nifedipine inhibited both noradrenaline and phenylephrine contractions. These results indicate that nifedipine is useful in differentiating contractile activity of vascular smooth muscle with respect to alpha-adrenoceptor agonism.
研究了硝苯地平（10⁻⁸和10⁻⁷M）对起搏诱导的心力衰竭犬背侧足背动脉和大隐静脉α-肾上腺素能反应的影响。两组犬的右心室以250次/分钟的频率起搏：第（1）组起搏1周（轻度心力衰竭），第（2）组平均起搏25.8天（重度心力衰竭高峰期）。硝苯地平对6-烯丙基-2-氨基-5,6,7,8-四氢-4H-噻唑并[4,5-d]氮杂䓬二盐酸盐（BHT 920）诱导的收缩具有非竞争性拮抗作用，且在相同程度上（即在对照、轻度心力衰竭和重度心力衰竭高峰期）发挥作用，其半数抑制浓度（IC50）值如下：背侧足背动脉分别为3.9（1.8 - 6.1）nM、4.4（1.2 - 8.4）nM和8.5（2.9 - 38.9）nM；大隐静脉分别为13.0（4.6 - 26.0）nM、13.0（7.3 - 18.6）nM和19.0（9.3 - 32.8）nM。在起搏开始前，硝苯地平对动脉或静脉中去甲肾上腺素或去氧肾上腺素产生的浓度-效应曲线无影响。起搏1周后，硝苯地平（10⁻⁷M）抑制了动脉和静脉中去甲肾上腺素诱导的收缩（动脉为70±5%，静脉为51±4%）。硝苯地平对去氧肾上腺素诱导的收缩无影响。在重度心力衰竭高峰期，硝苯地平抑制了去甲肾上腺素和去氧肾上腺素诱导的收缩。这些结果表明，硝苯地平在区分血管平滑肌对α-肾上腺素能激动剂的收缩活性方面是有用的。
