BAY-K-8644对猫大脑中动脉和股动脉收缩的影响。

The effects of BAY-K-8644 on the contraction of cat middle cerebral and femoral arteries.

作者信息

Salaices M, Marin J, Sanchez-Ferrer C F, Reviriego J

出版信息

Biochem Pharmacol. 1985 Sep 1;34(17):3131-5. doi: 10.1016/0006-2952(85)90158-3.

Abstract

The effects of BAY-K-8644 on the reactivity of cylindrical segments of cat middle cerebral and femoral arteries were studied. BAY-K-8644 induced dose-dependent contractile responses in cerebral arteries up to 10(-6) M; higher concentrations tended to cause relaxation of the segments. The dihydropyridine elicited contractions in femoral arteries only when these vessels were previously exposed to 15 mM K+. Nifedipine (3 X 10(-7) M) produced a parallel shift to the right of the dose-response curve to BAY-K-8644, whereas 5 X 10(-6)M verapamil markedly reduced the responses evoked by all concentrations of this drug. The removal of Ca2+ from the medium abolished the response evoked by the Ca2+-channel activator at 10(-7) M in both kinds of arteries. Under these conditions Ca2+ addition induced vasoconstriction, which was blocked by nifedipine (3 X 10(-7) M). Preincubation of femoral arteries with 10(-7) M BAY-K-8644 potentiated the effects evoked by 25, 50, 75 and 125 mM K+, but did not modify those produced by 10(-5) M noradrenaline. Nifedipine (10(-7) M and 3 X 10(-7) M) blocked the potentiation caused by this drug in a dose-dependent manner. Both the increase of the response elicited by BAY-K-8644 and the inhibitory effects of nifedipine were greater at 25 mM K+ than at 125 mM. These results suggest that BAY-K-8644 facilitates Ca2+ influx into smooth muscle through Ca2+ channels that are possibly voltage sensitive and the voltage independence of the drug-induced contractions in cerebral arteries.

摘要

研究了BAY-K-8644对猫大脑中动脉和股动脉圆柱状节段反应性的影响。BAY-K-8644在浓度高达10⁻⁶ M时可诱导大脑动脉产生剂量依赖性收缩反应；更高浓度则倾向于使节段舒张。仅当股动脉预先暴露于15 mM K⁺时，二氢吡啶才会引起其收缩。硝苯地平（3×10⁻⁷ M）使BAY-K-8644的剂量-反应曲线平行右移，而5×10⁻⁶ M维拉帕米则显著降低该药物所有浓度所诱发的反应。从培养基中去除Ca²⁺可消除两种动脉中10⁻⁷ M的Ca²⁺通道激活剂所诱发的反应。在这些条件下添加Ca²⁺会诱导血管收缩，而这可被硝苯地平（3×10⁻⁷ M）阻断。用10⁻⁷ M BAY-K-8644对股动脉进行预孵育可增强25、50、75和125 mM K⁺所诱发的效应，但不改变10⁻⁵ M去甲肾上腺素所产生的效应。硝苯地平（10⁻⁷ M和3×10⁻⁷ M）以剂量依赖性方式阻断该药物所引起的增强作用。BAY-K-8644所诱发反应的增强以及硝苯地平的抑制作用在25 mM K⁺时均比在125 mM时更大。这些结果表明，BAY-K-8644通过可能对电压敏感的Ca²⁺通道促进Ca²⁺流入平滑肌，以及该药物在大脑动脉中诱发收缩的电压非依赖性。