hexacyanoferrate-iii and linsidomine

SIN-1, a metabolite of the vasodilating drug molsidomine, was found to stimulate dose dependently (0.01-1 mM) soluble guanylate cyclase from bovine coronary arteries up to 100-fold the control value. The stimulatory effect of SIN-1 increased with rising concentrations of MnC1(2) or MgC1(2) and was diminished in the presence of methylene blue or ferricyanide. The time course of SIN-1-induced guanylate cyclase stimulation was characterized by a lag phase which was not observed after preincubation of the enzyme with SIN-1. In contrast to nitroglycerin and sodium nitroprusside, SIN-1 did not require the presence of cysteine or other thiols to stimulate guanylate cyclase. The results presented in this study provide further evidence that SIN-1 exerts its dilating effect on coronary vessels via direct stimulation of guanylate cyclase.

Topics: Animals; Cations, Divalent; Cattle; Coronary Vessels; Cyclic GMP; Ferricyanides; Guanylate Cyclase; In Vitro Techniques; Methylene Blue; Molsidomine; Muscle Relaxation; Muscle, Smooth, Vascular; Nitroglycerin; Nitroprusside; Oxadiazoles; Sodium Nitrite; Sulfhydryl Compounds; Sydnones