Tejerina T, Cauvin C, Tamargo J
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Eur J Pharmacol. 1992 Aug 25;219(2):279-84. doi: 10.1016/0014-2999(92)90306-o.
The inhibitory effects of the dihydropyridine Ca2+ antagonist, oxodipine, on contractions and 45Ca2+ influx stimulated by noradrenaline (NA) and high K+ in rabbit aorta were compared to the same parameters measured in mesenteric resistance arteries. In aortic rings oxodipine, 10(-11)-10(-6) M, inhibited in a concentration-dependent manner the contractions induced by high K+ (IC50 = 9.0 +/- 4.0 x 10(-10) M) or by Ca2+ in high K+ solution (IC50 = 6.2 +/- 2.4 x 10(-9) M), while responses to NA were only slightly affected (IC50 greater than 10(-6) M). In mesenteric resistance vessels oxodipine inhibited the contractions induced by high K+ and NA but was more effective against NA- than high K(+)-induced contractions (IC50 = 5.2 +/- 3.1 x 10(-10) and 1.2 +/- 1.8 x 10(-8) M, respectively). The concentration-inhibition curves for high K(+)-induced contraction and 45Ca2+ influx in aorta were almost superimposable (I50 = 2.2 +/- 2.0 x 10(-9) M), whereas NA-induced contractions were inhibited less than 45Ca2+ influx (I50 = 8.2 +/- 2.6 x 10(-8) M). In mesenteric resistance vessels the curves for contraction and 45Ca2+ influx stimulated by high K+ and NA were also superimposable, but 45Ca2+ influx stimulated by NA was more sensitive to oxodipine than that stimulated by high K+ (I50 = 3.9 +/- 2.0 x 10(-10) and 2.2 +/- 1.2 x 10(-8) M, respectively). It is concluded that the effects of oxodipine can be attributed to its ability to inhibit Ca2+ entry through both potential- and receptor-operated pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
将二氢吡啶类钙离子拮抗剂奥索地平对去甲肾上腺素(NA)和高钾刺激兔主动脉收缩及45Ca2+内流的抑制作用,与肠系膜阻力动脉中测量的相同参数进行比较。在主动脉环中,10(-11)-10(-6)M的奥索地平以浓度依赖方式抑制高钾(IC50 = 9.0 +/- 4.0 x 10(-10)M)或高钾溶液中钙离子(IC50 = 6.2 +/- 2.4 x 10(-9)M)诱导的收缩,而对NA的反应仅略有影响(IC50大于10(-6)M)。在肠系膜阻力血管中,奥索地平抑制高钾和NA诱导的收缩,但对NA诱导的收缩比对高钾诱导的收缩更有效(IC50分别为5.2 +/- 3.1 x 10(-10)和1.2 +/- 1.8 x 10(-8)M)。高钾诱导的主动脉收缩和45Ca2+内流的浓度-抑制曲线几乎重叠(I50 = 2.2 +/- 2.0 x 10(-9)M),而NA诱导的收缩比45Ca2+内流受抑制程度小(I50 = 8.2 +/- 2.6 x 10(-8)M)。在肠系膜阻力血管中,高钾和NA刺激的收缩和45Ca2+内流曲线也重叠,但NA刺激的45Ca2+内流比高钾刺激的对奥索地平更敏感(I50分别为3.9 +/- 2.0 x 10(-10)和2.2 +/- 上1.2 x 10(-8)M)。结论是奥索地平的作用可归因于其通过电压门控和受体门控途径抑制钙离子内流的能力。(摘要截短于250字)