Effects of chronic nitric oxide synthase inhibition on V'O 2max and exercise capacity in mice

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2017-03, Vol.390 (3), p.235
• Main Authors: Wojewoda, M, Przyborowski, K, Sitek, B, Zakrzewska, A, Mateuszuk, L, Zoladz, J A, Chlopicki, S
• Format: Article
• Language: English
• Subjects: 6-Ketoprostaglandin F1 alpha - blood; Adaptation, Physiological; Animals; Biomarkers - blood; Enzyme Inhibitors - pharmacology; Erythrocyte Count; Erythrocytes - drug effects; Erythrocytes - metabolism; Exercise Tolerance - drug effects; Hemoglobins - metabolism; Male; Mice, Inbred C57BL; NG-Nitroarginine Methyl Ester - pharmacology; Nitrates - blood; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitrites - blood; Oxygen Consumption - drug effects; Physical Exertion; Time Factors
• ISSN: 1432-1912
• DOI: 10.1007/s00210-016-1318-3

Acute inhibition of NOS by L-NAME (N -nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V'O ) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V'O and exercise performance have not been studied so far. In this study, we analysed the effect of L-NAME treatment, (LN2 and LN12, respectively) on V'O and exercise capacity (in maximal incremental running and prolonged sub-maximal incremental running tests), systemic NO bioavailability (plasma nitrite (NO ) and nitrate (NO )) and prostacyclin (PGI ) production in C57BL6/J mice. Mice treated with L-NAME for 2 weeks (LN2) displayed higher V'O and better running capacity than age-matched control mice. In LN2 mice, NO bioavailability was preserved, as evidenced by maintained NO plasma concentration. PGI production was activated (increased 6-keto-PGF plasma concentration) and the number of circulating erythrocytes (RBC) and haemoglobin concentration were increased. In mice treated with L-NAME for 12 weeks (LN12), NO bioavailability was decreased (lower NO plasma concentration), and 6-keto-PGF plasma concentration and RBC number were not elevated compared to age-matched control mice. However, LN12 mice still performed better during the maximal incremental running test despite having lower V'O . Interestingly, the LN12 mice showed poorer running capacity during the prolonged sub-maximal incremental running test. To conclude, short-term (2 weeks) but not long-term (12 weeks) treatment with L-NAME activated robust compensatory mechanisms involving preservation of NO2- plasma concentration, overproduction of PGI and increased number of RBCs, which might explain the fully preserved exercise capacity despite the inhibition of NOS.