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.

• Circadian rhythm
• Multiple sclerosis
• Uric acid
• Nitric oxide
• Carbon dioxide