Aoki K, Asano M
Br J Pharmacol. 1986 May;88(1):221-30. doi: 10.1111/j.1476-5381.1986.tb09490.x.
Vasoconstrictor effects of Bay K 8644 (an agonist known to increase Ca2+ influx through the voltage-dependent Ca2+ channels) on femoral arteries of 6 week old spontaneously hypertensive rats (SHR) were investigated, and data compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). The addition of Bay K 8644 (1 X 10(-10)-3 X 10(-7) M) elicited a dose-dependent contraction in SHR femoral artery in the absence of any contractile agent. Maximum contraction induced by this agonist was the same as the maximum induced by either K+-depolarization or alpha-adrenoceptor stimulation. Bay K 8644 was less effective in eliciting a contraction in the WKY femoral artery. Increased sensitivity to K+ was also observed in the SHR femoral artery. In contrast, contractions in response to alpha-adrenoceptor stimulation were the same in the SHR as those in the WKY. The addition of nifedipine, a Ca2+ channel antagonist, to an unstimulated preparation produced a dose-dependent relaxation in femoral arteries from SHR, but not from WKY. When the arteries were contracted with 60 mM K+, nifedipine produced similar relaxations in the SHR as those in the WKY, suggesting that the Ca2+ channels in the SHR femoral arteries are more activated than those in the WKY femoral arteries. Contractile responses to SHR femoral arteries to Bay K 8644 were antagonized competitively by nifedipine. Contractile responses to Ca2+ determined in K+-depolarized strips were also antagonized competitively by nifedipine. However, Schild plot analysis demonstrated a different pA2 value for nifedipine, suggesting that there may be a difference in the state of voltage-dependent Ca2+ channels in SHR femoral artery between the stimulation with Bay K 8644 and K+-depolarization.
研究了Bay K 8644（一种已知可通过电压依赖性钙通道增加钙离子内流的激动剂）对6周龄自发性高血压大鼠（SHR）股动脉的血管收缩作用，并将数据与年龄匹配的正常血压Wistar-Kyoto大鼠（WKY）的研究结果进行比较。在没有任何收缩剂的情况下，添加Bay K 8644（1×10⁻¹⁰ - 3×10⁻⁷ M）可引起SHR股动脉剂量依赖性收缩。该激动剂诱导的最大收缩与钾离子去极化或α-肾上腺素能受体刺激诱导的最大收缩相同。Bay K 8644在引发WKY股动脉收缩方面效果较差。在SHR股动脉中也观察到对钾离子的敏感性增加。相比之下，SHR对α-肾上腺素能受体刺激的收缩反应与WKY相同。向未刺激的制剂中添加钙通道拮抗剂硝苯地平可使SHR的股动脉产生剂量依赖性舒张，但对WKY则无此作用。当动脉用60 mM钾离子收缩时，硝苯地平在SHR中产生的舒张作用与在WKY中相似，这表明SHR股动脉中的钙通道比WKY股动脉中的钙通道更易被激活。硝苯地平竞争性拮抗SHR股动脉对Bay K 8644的收缩反应。在钾离子去极化条带中测定的对钙离子的收缩反应也被硝苯地平竞争性拮抗。然而，Schild图分析显示硝苯地平的pA2值不同，这表明在用Bay K 8644刺激和钾离子去极化时，SHR股动脉中电压依赖性钙通道的状态可能存在差异。
