Karaki H, Murakami K, Urakawa N
Arch Int Pharmacodyn Ther. 1986 Apr;280(2):230-40.
Mechanism of inhibitory action of sodium nitroprusside in vascular smooth muscle of rabbit aorta was examined. Sodium nitroprusside inhibited the 1 X 10(-6) M norepinephrine-induced contraction with IC50 (concentration to induce 50% inhibition) of 1.40 X 10(-7) M, but had little effect on the 65.4 mM K-induced contraction. In contrast, verapamil had little effect on the norepinephrine-induced contraction at the concentration needed to inhibit the high K-induced contraction. The inhibitory effect of sodium nitroprusside on the norepinephrine-induced contraction did not change in the verapamil-treated aorta. In the high K-solution with verapamil, norepinephrine induced a sustained contraction with similar magnitude as that in normal solution. Sodium nitroprusside also inhibited this contraction although the inhibitory effect was slightly less compared to that in the polarized aorta (IC50 = 2.90 X 10(-7) M, p less than 0.01). In a Ca-deficient solution, norepinephrine induced a transient contraction due to release of cellular Ca. Sodium nitroprusside inhibited the norepinephrine-induced transient contraction at slightly higher concentrations than those which inhibit the sustained contraction (IC50 = 5.55 X 10(-7) M). In a high K, Ca deficient solution, norepinephrine also induced a transient contraction. The inhibitory effect of sodium nitroprusside on the transient contraction was reduced in the depolarized aorta (IC50 = 9.50 X 10(-6) M). It is suggested that the inhibition of norepinephrine-induced sustained contraction by sodium nitroprusside is mainly due to the direct inhibitory effect on the receptor linked-Ca channels whereas the inhibition of norepinephrine-induced transient contraction is attributable mainly to membrane hyperpolarization and, at higher concentrations, to a direct inhibition of Ca release.
研究了硝普钠对兔主动脉血管平滑肌的抑制作用机制。硝普钠抑制1×10⁻⁶ M去甲肾上腺素诱导的收缩，IC₅₀（诱导50%抑制的浓度）为1.40×10⁻⁷ M，但对65.4 mM钾诱导的收缩几乎没有影响。相比之下，维拉帕米在抑制高钾诱导的收缩所需浓度下，对去甲肾上腺素诱导的收缩几乎没有影响。在维拉帕米处理的主动脉中，硝普钠对去甲肾上腺素诱导的收缩的抑制作用没有改变。在含有维拉帕米的高钾溶液中，去甲肾上腺素诱导的持续收缩幅度与正常溶液中相似。硝普钠也抑制这种收缩，尽管与极化主动脉相比，抑制作用略小（IC₅₀ = 2.90×10⁻⁷ M，p < 0.01）。在缺钙溶液中，去甲肾上腺素由于细胞内钙的释放而诱导短暂收缩。硝普钠抑制去甲肾上腺素诱导的短暂收缩的浓度略高于抑制持续收缩的浓度（IC₅₀ = 5.55×10⁻⁷ M）。在高钾、缺钙溶液中，去甲肾上腺素也诱导短暂收缩。在去极化的主动脉中，硝普钠对短暂收缩的抑制作用减弱（IC₅₀ = 9.50×10⁻⁶ M）。提示硝普钠对去甲肾上腺素诱导的持续收缩的抑制主要是由于对受体偶联钙通道的直接抑制作用，而对去甲肾上腺素诱导的短暂收缩的抑制主要归因于膜超极化，在较高浓度下还归因于对钙释放的直接抑制。
