Asano M, Aoki K, Matsuda T
J Pharmacol Exp Ther. 1986 Oct;239(1):198-205.
Agonist actions of methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate (Bay k 8644) were investigated in femoral and mesenteric arteries from 6-week-old spontaneously hypertensive rats (SHRs), and data compared with findings in normotensive Wistar-Kyoto rats (WKYs). The addition of Bay k 8644 produced a dose-dependent contraction in SHR femoral artery with a pD2 value of 8.55. Maximum contraction induced by this agonist (1 X 10(-7) M) was comparable to the maximum developed by K+-depolarization. Bay k 8644 was much less effective in eliciting the contractile responses on WKY femoral artery. Contractile responses of mesenteric and tail arteries to Bay k 8644 were weak and were not significantly different between SHR and WKY. Thoracic aorta was sensitive to the contractile response to Bay k 8644, but the sensitivity was not significantly different between SHR and WKY. Increased responsiveness to exogenously applied K+ was also observed in SHR femoral artery as compared to WKY. Contractile responses of SHR femoral artery to Bay k 8644 were antagonized competitively by nifedipine (pA2 = 8.36), a dihydropyridine Ca++ antagonist, but noncompetitively by diltiazem, a non-dihydropyridine Ca++ antagonist. When the effect of nifedipine on the dose-response curve for Bay k 8644 was determined in WKY femoral artery, there was a similar extent of rightward displacement of the dose-response curve to that seen in SHR. Nifedipine was less efficacious in relaxing the contractile response to Bay k 8644 compared to the contractile response to K+ in SHRs femoral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了甲基-1,4-二氢-2,6-二甲基-3-硝基-4-(2-三氟甲基苯基)-吡啶-5-羧酸酯（Bay k 8644）对6周龄自发性高血压大鼠（SHR）股动脉和肠系膜动脉的激动剂作用，并将数据与正常血压的Wistar-Kyoto大鼠（WKY）的研究结果进行比较。加入Bay k 8644后，SHR股动脉产生剂量依赖性收缩，pD2值为8.55。该激动剂（1×10⁻⁷ M）诱导的最大收缩与K⁺去极化诱导的最大收缩相当。Bay k 8644对WKY股动脉引起收缩反应的效果要差得多。肠系膜动脉和尾动脉对Bay k 8644的收缩反应较弱，SHR和WKY之间无显著差异。胸主动脉对Bay k 8644的收缩反应敏感，但SHR和WKY之间的敏感性无显著差异。与WKY相比，SHR股动脉对外源性K⁺的反应性也增加。SHR股动脉对Bay k 8644的收缩反应被二氢吡啶类钙拮抗剂硝苯地平竞争性拮抗（pA2 = 8.36），但被非二氢吡啶类钙拮抗剂地尔硫卓非竞争性拮抗。当在WKY股动脉中测定硝苯地平对Bay k 8644剂量反应曲线的影响时，剂量反应曲线的右移程度与SHR中观察到的相似。与SHR股动脉中对K⁺的收缩反应相比，硝苯地平在舒张对Bay k 8644的收缩反应方面效果较差。（摘要截短于250字）
