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Cardiovascular Aging

Aging enhances pressure-induced arterial superoxide formation

¹Department of Physiology, New York Medical College, Valhalla, New York; and ²Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, China

Submitted 3 April 2007 ; accepted in final form 6 June 2007

The purpose of this study was to investigate the mechanisms that regulate superoxide (O₂^–) production as a function of an acute elevation of intravascular pressure and age. Mesenteric arteries isolated from young (6 mo) and aged (24 mo) male Fischer 344 rats were used. O₂^– production in vessels in response to 80 (normal pressure, NP) and 180 (high pressure, HP) mmHg was determined by the superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction assay. In vessels exposed to NP, O₂^– production was significantly higher in aged than in young vessels (32.7 ± 7.0 vs. 15.4 ± 2.4 nmol·mg^–1·30 min^–1). HP enhanced O₂^– production in vessels of both groups, but the enhancement was significantly greater in aged than in young vessels (63.4 ± 6.7 vs. 32.7 ± 4.3 nmol·mg^–1·30 min^–1). Apocynin (100 µmol/l) attenuated HP-induced increases in O₂^– production in both groups, whereas allopurinol (100 µmol/l) and N-nitro-L-arginine methyl ester (100 µmol/l) inhibited the response only in aged vessels. Confocal microscopy showed increases in O₂^– in response to HP in endothelial and smooth muscle layers of both groups, with much greater fluorescent staining in aged than in young rats and in the endothelium than in smooth muscle cells. No significant changes in NAD(P)H oxidase gene and protein expressions were observed in vessels of the two groups. Upregulation of protein expression of xanthine oxidase was detected in aged vessels. We conclude that NAD(P)H oxidase contributes importantly to HP-induced enhanced O₂^– production in vessels of both young and aged rats, whereas xanthine oxidase and nitric oxide synthase-dependent O₂^– production also contribute to the enhancement in mesenteric arteries of aged rats.

endothelium; reactive oxygen species; NAD(P)H oxidase; xanthine oxidase; endothelial nitric oxide synthase uncoupling

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				C. Yan, A. Huang, G. Kaley, and D. Sun Chronic high blood flow potentiates shear stress-induced release of NO in arteries of aged rats Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3105 - H3110. [Abstract] [Full Text] [PDF]