Aging enhances pressure-induced arterial superoxide formation

Abstract

The purpose of this study was to investigate the mechanisms that regulate superoxide (O(2)(*-)) 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. O(2)(*-) 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, O(2)(*-) 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 O(2)(*-) 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 micromol/l) attenuated HP-induced increases in O(2)(*-) production in both groups, whereas allopurinol (100 micromol/l) and N(omega)-nitro-L-arginine methyl ester (100 mumol/l) inhibited the response only in aged vessels. Confocal microscopy showed increases in O(2)(*-) 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 O(2)(*-) production in vessels of both young and aged rats, whereas xanthine oxidase and nitric oxide synthase-dependent O(2)(*-) production also contribute to the enhancement in mesenteric arteries of aged rats.

Elevated Blood Pressure in Preterm-Born Offspring Associates With a Distinct Antiangiogenic State and Microvascular Abnormalities in Adult Life

“…11,12,27 Experimental elevation in blood pressure can directly lead to capillary rarefaction, most likely through an effect of increased generation of endothelial-derived reactive oxygen species on microvascular integrity. 28,29 Capillary rarefaction can also antedate the onset of hypertension because reduced capillary density is observed in normotensive individuals at high risk of developing hypertension. 12 However, capillary rarefaction is not a generalized observation in those predisposed to hypertension.…”

Alterations of store-operated calcium entry and cyclopiazonic acid-induced endothelium-derived relaxations in aging rat thoracic aorta

“…Contradictory data exist on age-related changes on eNOS expression and NO production such that some show downregulation (5,14,52,58), while others suggest upregulation (22,60). Furthermore, increased production of reactive oxygen species were also reported during aging (14,24,27,48,60). Enhanced production of vasoconstricting factors also contributes to age-related endothelial dysfunction (5,37,38).…”

Mechanisms of Superoxide Signaling in Epigenetic Processes: Relation to Aging and Cancer

“…Chen et al showed the age-related increase in mitochondrial superoxide production in the testosteroneproducing cells of Brown Norway rat testes [55]. Superoxide production by xanthine oxidase and NO synthase in mesenteric arteries from aged rats was higher than in young ones [56].…”