Isolated coronary artery responses to Ach (1×10−10–1×10−5
M
) in SMP30 KO and WT mice in an organ chamber. ACh-induced vasoconstriction appeared in the SMP30 KO mice. The NOS inhibitor, Nω-nitro-l-arginine-methyl ester (L-NAME) (0.3 mM), did not further enhance this response. In the WT mice, ACh-induced vasodilation appeared, blunted with L-NAME (A). BH4 (1 μM) did not change ACh-induced vasoconstriction in the SMP30 KO mice (B). ACh-induced vasoconstriction in the SMP30 KO mice changed to vasodilation with the thiol-reducing agent, dithiothreitol (DTT) (0.1 μM) (C). Inhibition of glutathione reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (80 μM) decreased ACh-induced vasodilation, which was restored by DTT in the WT mice (D). Values were expressed as means±S.E.M., n=10, each, *p<0.01.