Differential effects of nitric oxide synthase inhibitors on endothelium-dependent and nitrergic nerve-mediated vasodilatation in the bovine ciliary artery.
OBJECTIVE
We have previously demonstrated that L-NMMA (NG-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-[aminoethyl]aminopentyl-N'-nitroguanidine) and L-NPA (NG-propyl-L-arginine), produced selective blockade of vasodilatation induced by nitrergic nerves but not endothelium-derived nitric oxide.


METHODS
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.


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 (NG-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
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.
Overend
J
J
Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, UK.
Martin
W
W
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D019842:Ciliary Arteries / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009213:Myography; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; C073754:omega-N-cyclopropylarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester