NADPH-induced contractions of mouse aorta do not involve NADPH Oxidase: A role for P2X receptors

Judkins, C. P., Sobey, C. G., Dang, T. T., Miller, A. A. , Dusting, G. J. and Drummond, G. R. (2006) NADPH-induced contractions of mouse aorta do not involve NADPH Oxidase: A role for P2X receptors. Journal of Pharmacology and Experimental Therapeutics, 317(2), pp. 644-650. (doi: 10.1124/jpet.105.096610) (PMID:16407465)

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Abstract

Reactive oxygen species elicit vascular effects ranging from acute dilatation because of hydrogen peroxide-mediated opening of K+ channels to contraction arising from superoxide-dependent inactivation of endothelium-derived nitric oxide. Given that NADPH oxidases are major sources of superoxide in the vascular wall, this study examined the effects of exogenous NADPH, a substrate of these enzymes, on superoxide generation and isometric tone in mouse isolated aortic rings. NADPH caused concentration-dependent increases in superoxide generation (measured by lucigenin-enhanced chemiluminescence) and vascular tone (isometric tension recordings). However, surprisingly, whereas oxidized NADP+ was unable to support superoxide production, it was equally as effective as reduced NADPH at stimulating vasocontraction. In addition, an NADPH oxidase inhibitor, diphenyleneiodonium, markedly attenuated NADPH-induced superoxide production, yet had no effect on vasocontractions to NADPH. In contrast, a broad specificity P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid, as well as the P2X1 selective antagonist, NF023, markedly attenuated both endothelium-dependent and -independent vasocontractions to NADPH, as did the P2X-desensitizing agent α,β-methylene-ATP. Importantly, α,β-methylene-ATP had no effect on superoxide production induced by NADPH. In conclusion, these findings suggest little role for NADPH oxidase-derived superoxide in the contractile effects of NADPH in the mouse aorta. Rather, NADPH seems to act as an agonist at two distinct P2X receptor populations; one located on the endothelium and the other on smooth muscle layer, both of which ultimately lead to contraction.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Miller, Dr Alyson
Authors: Judkins, C. P., Sobey, C. G., Dang, T. T., Miller, A. A., Dusting, G. J., and Drummond, G. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Pharmacology and Experimental Therapeutics
Publisher:ASPET
ISSN:0022-3565
ISSN (Online):1521-0103

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