Mechanism of inhibitory action of sodium nitroprusside in vascular smooth muscle of rabbit aorta.
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.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D005292:Ferricyanides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D005292:Ferricyanides; D009599:Nitroprusside; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine