期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 29, 期 6, 页码 1130-1137出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2009.37
关键词
acetylcholine; basilar artery; cerebral arterioles; microcirculation; reactive oxygen species
资金
- National Institutes of Health [HL-38901, NS-24621, HL-62984, HL-63943]
- American Heart Association in the form of a Bugher Award [0575092N]
- University of Iowa
Although arachidonic acid (AA) has diverse vascular effects, the mechanisms that mediate these effects are incompletely defined. The goal of our study was to use genetic approaches to examine the role of hydrogen peroxide (H2O2), glutathione peroxidase (Gpx1, which degrades H2O2), and CuZn-superoxide dismutase (SOD1, which produces H2O2 from superoxide) in mediating and in determining vascular responses to AA. In basilar arteries in vitro, AA produced dilation in nontransgenic mice, and this response was reduced markedly in transgenic mice overexpressing Gpx1 (Gpx1 Tg) or in those genetically deficient in SOD1. For example, AA (1 nmol/L to 1 mu mol/L) dilated the basilar artery and this response was reduced by similar to 90% in Gpx1 Tg mice (P < 0.01), although responses to acetylcholine were not altered. Dilation of cerebral arterioles in vivo in response to AA was inhibited by B50% by treatment with catalase (300 U/mL) (P < 0.05) and reduced by as much as 90% in Gpx1 Tg mice compared with that in controls (P<0.05). These results provide the first evidence that Gpx1 has functional effects in the cerebral circulation, and that AA-induced vascular effects are mediated by H2O2 produced by SOD1. In contrast, cerebral vascular responses to the endothelium-dependent agonist acetylcholine are not mediated by H2O2. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1130-1137; doi:10.1038/jcbfm.2009.37; published online 8 April 2009
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