Effect of age on electrical field stimulation (EFS)-induced endothelium-dependent vasodilation in male and female rats

Objective: The purpose of this study was to determine whether the effect of age on electrical field stimulation (EFS)-induced endothelium-dependent vasodilation was different in males and females. Methods: Young (3 month) and old (25 month) Fisher 344 rats were studied: young females (YF, n=34), young males (YM, n=28), old females (OF, n=19), and old males (OM, n=24). Isolated mesenteric resistance arteries (endothelium-intact and denuded) were pressurized, and outer diameter was monitored. EFS-response curves (0.1-8 Hz) were performed in preconstricted arteries in the presence of guanethidine. EFS responses were expressed as percent relaxation from preconstricted diameter. Area under the curve (AUC) was calculated and comparisons were made using ANOVA and t-tests. Results: Males became less responsive to EFS-induced vasodilation with age, while responses among females were unaffected (AUC: YM=344±23, OM=253±25, P=0.008; YF=397±21, OF=365±25, P=0.33). Endothelial denudation produced a significant decrease in EFS-induced dilation among all rat groups. The effect of denudation was greater in young animals compared to old. Incubation with the nitric oxide synthase inhibitor Nω-nitro-L-arginine (LNA) significantly decreased EFS responsiveness among all of the rat groups. Conclusions: EFS-induced vasodilation declines with age among males. In YF and YM endothelium-dependent EFS-induced vasodilation is mediated by the release of endothelium-derived NO. With age, endothelial function declines, which is likely due to a decrease in the production of endothelium-derived NO. A decline in endothelial-derived NO is likely responsible for the decrease in EFS-induced vasodilation with age among males.