Aging enhances pressure-induced arterial superoxide formation

Area of Science:

• Cardiovascular Physiology
• Aging Research
• Oxidative Stress Mechanisms

Background:

• Superoxide (O(2)(*-)) production is implicated in vascular dysfunction.
• Age-related changes and elevated intravascular pressure can impact vascular oxidative stress.

Purpose of the Study:

• To investigate the mechanisms regulating superoxide production in response to acute increases in intravascular pressure and aging.
• To compare superoxide production in young and aged rat mesenteric arteries under normal and high pressure conditions.

Main Methods:

• Mesenteric arteries from young and aged Fischer 344 rats were subjected to normal (80 mmHg) and high (180 mmHg) pressure.
• Superoxide production was quantified using the nitroblue tetrazolium assay.
• Involvement of specific enzymes was assessed using inhibitors like apocynin, allopurinol, and N(omega)-nitro-L-arginine methyl ester.
• Confocal microscopy evaluated superoxide localization.
• Gene and protein expression of NAD(P)H oxidase and xanthine oxidase were analyzed.

Main Results:

• Aged vessels exhibited higher basal superoxide production than young vessels.
• High pressure significantly increased superoxide production in both age groups, with a greater effect in aged rats.
• Apocynin attenuated high pressure-induced superoxide production in both groups.
• Allopurinol and N(omega)-nitro-L-arginine methyl ester inhibited superoxide production only in aged vessels.
• Confocal microscopy revealed increased superoxide in endothelial and smooth muscle cells, particularly in aged rats.
• Upregulation of xanthine oxidase protein expression was observed in aged vessels.

Conclusions:

• NAD(P)H oxidase is a significant contributor to high pressure-induced superoxide production in rat mesenteric arteries across age groups.
• In aged rats, xanthine oxidase and nitric oxide synthase also contribute to the elevated superoxide production under high pressure conditions.
• Aging exacerbates the vascular response to increased intravascular pressure, involving multiple enzymatic pathways for superoxide generation.