Objectives: 

Aging is associated with changes in the vascular system that can lead to endothelial dysfunction. We have investigated the effects of aging on vascular reactivity to U46619, a stable analog of thromboxane A2 (TXA2), in small mesenteric arteries from female senescence-accelerated mice (SAMP8), a murine model of aging.

Materials: 

Two-millimeter segments of small mesenteric arteries (~200 mm internal diameter) from female SAMP8 mice of 3-, 6- and 10-months old (n=8 per group) were mounted in a wire myograph for isometric recording of tension and concentration response curves for U46619 were performed in the absence and in the presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Branches of the mesenteric artery were immediately frozen for protein expression analysis and a sample of blood was collected. Differences among experimental groups were analysed by one-way ANOVA, followed by Bonferroni's post-test.

Results: 

At 3 months old, U46619 (10-9 to 3x10-7 M) induced concentration-dependent contractions in small mesenteric arteries with an EC50 of 2.7×10-8 M and a maximal contraction (Emax) of 497±53 mg. Aging increased progressively Emax and decreased EC50 values. At 3 months old, L-NAME (10-4 M) increased Emax and decreased EC50 values to U46619. A decreased NO contribution to TXA2-induced contractions was noticed at 6 months of age. At 10 months old, L-NAME did not modify contractions induced by U46619. Supporting these data, biochemical studies revealed an aging-associated decrease of NO bioavailability.

Conclusions: 

This study provides evidences that TXA2–dependent contraction is enhanced by aging in small mesenteric arteries involving a decreased NO bioavailability. These mechanisms might be relevant in the understanding of the effects of aging on resistance arteries function.

Supported by Min. Economía y Competitividad (PRI-AIBDE-2011-0855), ISCIII (FIS 10/00518, RED HERACLES RD06/0009), Generalitat Valenciana (ACOMP/2012/218), Spain.