Nitric oxide synthase derived plasma nitrite predicts exercise capacity

Tienush Rassaf ^1*, Thomas Lauer ¹, Christian Heiss ², Jan Balzer ¹, Sarah Mangold ¹, Thorsten Leyendecker ¹, Jessica Rottler ¹, Christine Drexhage ¹, Christian Meyer ¹ and Malte Kelm ¹

¹ University of Aachen, Germany
² University of California, SF, United States

^* To whom correspondence should be addressed. E-mail: rassaf{at}gmx.de.

Accepted 27 April 2007

Abstract

Background: Nitrite is the main oxidation product of nitric oxide (NO) in plasma. It sensitively reflects changes in endothelial NO-synthase (eNOS) activity under fasting conditions and serves as an endocrine NO donor contributing to the regulation of blood flow through reaction with hemoglobin. Since NO is necessary to maintain an adequate vascular response to the increased demands of blood flow, NO is believed to be important for vasodilation induced by exercise.

Objective: We have focused on the question whether the capacity of the vasculature to produce nitrite is associated with exercise performance.

Design: Using chemiluminescence-detection we studied nitrite levels in 55 healthy subjects (40±2 years, 22 males) before and after exercise test and determined endothelial function measuring flow- mediated-dilation of the brachial artery using high-resolution ultrasound. In a subset, the NOS-inhibitor NG-monomethyl-L-arginine (L-NMMA) was applied to elucidate the impact of eNOS on changes in nitrite.

Results: Exercise increased plasma nitrite from 97±6 to 125±8 nmol/L (p<0.001). The relative increase in plasma nitrite was related to FMD (6.1±0.3%) r= 0.36; p=0.01). L-NMMA blocked increases of nitrite. The post-exercise nitrite concentration correlated with exercise performance as determined by maximally reached stress power in Watt (r=0.37; p<0.007) and inversely with age. Multivariate analysis showed that both age and post-exercise nitrite levels were independent predictors of stress endurance and power.

Conclusion: The present results suggest a role of plasma nitrite in the adaption of hemodynamics during exercise. An impaired increase in plasma nitrite levels may limit exercise capacity.

Key Words: exercise, nitric oxide, nitrite

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