Abstract 350: Metabolism of Nitrite and Sulfide in the Aging Cardiovascular System

Abstract

Introduction: Hydrogen Sulfide (H2S) and Nitric Oxide (NO) are gaseous signaling molecules that affect many pathophysiological functions like vasodilation, anti-inflammation, cytoprotection, anti-apoptosis, mitochondrial respiration and angiogenesis. These actions suggest that the relationship between these gasotransmitters could be involved in the cardiovascular aging response. Objective: We examined the age dependent regulation of H2S and NO metabolites in mice. Methods: Levels of H2S and NO metabolites were measured in various organs of C57BL/6J wild type mice at age 6, 12 and 24 weeks. The monobromobimane (MBB)-HPLC method was used to measure various sulfide pools. NO metabolites were measured using NO chemiluminescence. One-way ANOVA with bonferroni post-testing was used to compare metabolites between age groups. A p value of ≤ 0.05 was considered significant. Results: In the heart, lung and kidneys there was a significant increase in total and free sulfide levels with age over 24 weeks. In the heart, bound sulfide and acid labile sulfide remained stable with age. In the kidney, the bound sulfide increased with age and acid labile sulfide remained stable. In the lung, bound sulfide remained stable and acid labile sulfide remained stable with age. In the aorta and mesenteric artery, tissue total sulfide levels decreased with age. Lastly, the ratio between total H2S versus NO significantly increased with age in the heart and kidney. Conclusion: Our study reveals novel relationships between cardiovascular H2S and NO metabolism during aging. The increased H2S/NO ratio during aging may indicate important biochemical changes that affect cardiovascular pathogenesis.