Differential effects of nitric oxide synthase inhibitors on endothelium-dependent and nitrergic nerve-mediated vasodilatation in the bovine ciliary artery

Background and purpose: We have previously demonstrated that L-NMMA (N-G-monomethyl-L-arginine) selectively inhibits vasodilatation produced by endothelium-derived nitric oxide but not nitrergic nerves in the bovine penile artery. The present study investigated whether L-NMMA had a similar selective action in the bovine ciliary artery. We also investigated whether two recently introduced inhibitors of neuronal nitric oxide synthase (nNOS), AAAN (N-(4S)-4-amino-5-[amino-ethyl] aminopentyl-N'-nitroguanidine) and L-NPA (N-G-propyl-L-arginine), produced selective blockade of vasodilatation induced by nitrergic nerves but not endothelium-derived nitric oxide. Experimental approach: Rings of bovine ciliary artery were suspended in a wire myograph for tension recording. Neurogenic ( nitrergic) vasodilatation was elicited by electrical field stimulation, and endothelium-dependent, nitric oxide-mediated dilatation was evoked using bradykinin. Key results: L-NMMA inhibited vasodilatation induced by endothelium-derived nitric oxide but not the nitrergic nerves. In fact, L-NMMA, acted like L-arginine in protecting nitrergic vasodilatation against inhibition by L-NAME (N-G-nitro-L-arginine methyl ester). AAAN had no effect on vasodilatation induced by either nitrergic nerves or endothelium-derived nitric oxide, but L-NPA inhibited both with equal potency. Conclusions and implications: In the bovine ciliary artery, L-NMMA acts as a selective inhibitor of the vasodilatation induced via endothelial NOS, without affecting that operating via nNOS. Furthermore, the putative nNOS inhibitors, AAAN and L-NPA failed to produce the expected selective inhibition of nitrergic vasodilatation in this artery.