Premium
Superoxide from uncoupled nitric oxide synthase reduces endothelium‐dependent arteriolar dilation in mice fed high salt
Author(s) -
Boegehold Matthew A.,
Nurkiewicz Timothy R.
Publication year - 2009
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.23.1_supplement.952.16
Subject(s) - nitric oxide , superoxide , nitric oxide synthase , endocrinology , medicine , chemistry , dilator , vasodilation , tetrahydrobiopterin , nitrite , endothelium , acetylcholine , biochemistry , biology , enzyme , organic chemistry , nitrate
We have previously reported that the impaired endothelium‐dependent dilation of arterioles in rodents on a high salt diet is due to oxidation of nitric oxide (NO) by superoxide anion (O 2 − ) in the arteriolar wall. The aim of this study was to test the hypothesis that "uncoupled" nitric oxide synthase (NOS) is the predominant source of this O 2 − . Arterial pressure in C57BL/6J mice fed a high salt (4%, HS) diet for 4 weeks was not significantly different from that in mice fed a normal salt (0.45%, NS) diet. However, compared to NS mice, spinotrapezius muscle arterioles in HS mice had elevated arteriolar wall oxidant activity (assessed by hydroethidine oxidation) and a large (75‐80%) reduction in dilator responses to acetylcholine. In HS mice, arteriolar oxidant stress was abolished by acute application of the NOS inhibitor N G monomethyl L‐arginine and by long‐term supplementation of L‐arginine intake (1.51% in drinking water for 4 weeks), which has been shown to increase vascular tetrahydrobiopterin (BH 4 ) levels. L‐arginine supplementation also prevented the reduction in arteriolar ACh responses in HS mice but had no effect on these responses in NS mice. These findings suggest that NOS uncoupling due to reduced BH 4 availability is primarily responsible for O 2 − accumulation and the resultant impairment of NO‐dependent arteriolar dilation in mice fed a high salt diet. (Support AHA Grant‐in‐Aid 0755264B and NIH ES‐015022)