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

Authors

  • J Overend,

    1. Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, UK
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  • W Martin

    Corresponding author
    1. Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, UK
      Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK. E-mail: W.Martin@bio.gla.ac.uk
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Division of Neuroscience & Biomedical Systems, Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK. E-mail: W.Martin@bio.gla.ac.uk

Abstract

Background and purpose:

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.

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 (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 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.

British Journal of Pharmacology (2007) 150, 488–493. doi:10.1038/sj.bjp.0707113

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