Differential Effects of Nitric Oxide Synthase Inhibitors in Rats

We investigated the action of NOS inhibitors on NOS in rats. Both of nitric oxide synthase inhibitors, $N^G$-monomethyl-L-arginine $(L-NMMA,\;3\;{\mu}M)$ or $N^G$-nitro-L-arginine methylester $(L-NAME,\;30\;{\mu}M),$ augmented phenylephrine $(PE,\;10^{-7}\;M)-induced$ contraction which was inhibited by acetylcholine (ACh) in rat thoracic aorta. This augmentation by L-NAME or L-NMMA was attenuated with the treatment of NO precursor, arginine. ACh, however, decreased the augmentation induced by L-NMMA, but not by L-NAME. Superoxide dismutase (SOD, 50 u/ml) potentiated an inhibitory effect of ACh on the PE $(10^{-7}\;M)-induced$ contraction. It has been known that platelet activating factor itself induces iNOS. Platelet activating factor $(PAF,\;10^{-7}\;M)$ inhibited PE $(10^{-7}\;M)-induced$ contraction. Pretreatment with L-NMMA (30 mM) or L-NAME (30 mM) significantly blocked the inhibitory action of PAF on PE-induced contraction. L-NMMA (100 mM) or L-NAME (100 mM) reduced nerve conduction velocity (NCV) relevant to nNOS in rat sciatic nerve. ACh attenuated the reduction of NCV by L-NMMA-, but not by L-NAME-induced reduction of NCV. These results suggest that L-NMMA and/or L-NAME have different action on three types of NOS in rats.