Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly

Background: Peritoneal dialysis solution (PDS) dilates peritoneal microvessels predominantly by the activation of the endothelial nitric oxide (NO) pathway. We made an incidental observation of decreased PDS-induced, NO-dependent peritoneal microvascular vasoreactivity in elderly rats naïve to PDS exposure. We hypothesized that this subordinate NO-mediated peritoneal microvascular vasoreactivity is caused by increased oxidative stress in the aged endothelium, which compromises NO bioavailability in the elderly, and that peritoneal microvascular vasoreactivity can be improved by the supplementation of antioxidant glycine to PDS. Methods: We studied PDS-mediated vasoreactivity of four intestinal visceral arterioles of different orders by in vivo intravital microscopy in weaned, adult, and elderly rats to (i) confirm subordinate vasoreactivity to PDS in elderly rats; (ii) restore vasoreactivity by glycine supplementation; and (iii) establish age as an independent risk factor for endothelial cell dysfunction. Results: In a crossover series, peritoneal microvascular vasoreactivity to PDS exposure was remarkably decreased in elderly rats. This subordinate vasoreactivity was completely restored by the supplementation of glycine to PDS. In a separate series, we assessed in situ endothelial cell function in weaned and adult rats using the cumulative acetylcholine concentration-response curves. Unlike the adults, the weaned rats demonstrated remarkable sensitivity and reactivity to cumulative acetylcholine concentrations, suggesting the dependency of endothelial cell function on age. Conclusion: Aging is an independent risk factor for peritoneal microvascular endothelial cell dysfunction. Endothelial function in the elderly can be recovered by reinforcing the bioavailability of endothelial-derived NO through glycine. Dietary glycine supplementation is a potential therapeutic strategy to decrease the burden of oxidative stress on the aged endothelium.