Altered Circadian Relationship Between Serum Nitric Oxide, Carbon Dioxide, and Uric Acid in Multiple Sclerosis

Abstract

The free radical nitric oxide (NO·) is involved in a variety of diverse biological processes from acting as a vasodilator in the cardiovascular system to being the rate-limiting component in the production of peroxynitrite (ONOO−), a contributor to neurodegenerative disorders such as multiple sclerosis (MS). Uric acid (UA), the end product of purine metabolism in humans and a selective inhibitor of toxic reactions attributed to radicals formed by the interaction of ONOO− and CO2, is generally low in MS patients. We investigated the relationship between serum ONOO−, CO2, and UA in MS patients and normal controls by comparing the circadian characteristics of the NO· metabolites nitrite/nitrate (NO), CO2, and UA. In this preliminary study, we found the functional relationship ascribed to the circadian timing of the peak and trough levels of NO, CO2, and UA in healthy subjects to be clearly altered in MS patients. These findings suggest that alterations in the temporal relationship between the 24 h pattern in serum ONOO− formation and UA may either contribute to or reflect the disease processes in MS.