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NADPH‐induced contractions of mouse aorta do not involve NADPH oxidase: A role for P2X receptors
Author(s) -
Drummond Grant R,
Judkins Courtney P,
Dang Thuy T,
Miller Alyson A,
Dusting Gregory J,
Sobey Christopher G
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a664-a
Subject(s) - nadph oxidase , superoxide , chemistry , lucigenin , nox4 , reactive oxygen species , vascular smooth muscle , contraction (grammar) , receptor , methylene blue , nitric oxide , endothelium , biochemistry , medicine , biophysics , enzyme , endocrinology , biology , organic chemistry , photocatalysis , smooth muscle , catalysis
Reactive oxygen species elicit vascular effects ranging from dilatation due to hydrogen peroxide‐mediated opening of K + channels, to contraction arising from superoxide (O 2 − ) ‐dependent inactivation of endothelium‐derived nitric oxide. Given that NADPH oxidases are major sources of O 2 − in the vascular wall, this study examined the effects of exogenous NADPH, a substrate of these enzymes, on O 2 − generation (lucigenin) and vascular tone (isometric tension) in mouse isolated aortic rings. NADPH caused concentration‐dependent increases in O 2 − generation and vascular tone. However, while oxidised NADP + was unable to support O 2 − production, it was equally as effective as reduced NADPH at stimulating contraction. An NADPH oxidase inhibitor, diphenyleneiodonium, markedly attenuated NADPH‐induced O 2 − production, yet had no effect on contractions to NADPH. In contrast, two P2X receptor antagonists, PPADS and NF023, markedly attenuated both endothelium‐dependent and ‐independent contractions to NADPH, as did the P2X desensitising agent, α,β‐methylene‐ATP. Importantly, α,β‐methylene‐ATP had no effect on O 2 − production induced by NADPH. In conclusion, these findings suggest little role for NADPH oxidase‐derived O 2 − in the contractile effects of NADPH in the mouse aorta. Rather, NADPH acts as an agonist at two P2X receptor populations; one located on the endothelium and the other on smooth muscle layer.