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Effects of chronic nitric oxide synthase inhibition on V’O2max and exercise capacity in mice

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Abstract

Acute inhibition of NOS by L-NAME (Nω-nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V’O2max) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V’O2max 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’O2max and exercise capacity (in maximal incremental running and prolonged sub-maximal incremental running tests), systemic NO bioavailability (plasma nitrite (NO2 −) and nitrate (NO3 −)) and prostacyclin (PGI2) production in C57BL6/J mice. Mice treated with L-NAME for 2 weeks (LN2) displayed higher V’O2max and better running capacity than age-matched control mice. In LN2 mice, NO bioavailability was preserved, as evidenced by maintained NO2 − plasma concentration. PGI2 production was activated (increased 6-keto-PGF1α 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 NO2 − plasma concentration), and 6-keto-PGF1α 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’O2max. 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 PGI2 and increased number of RBCs, which might explain the fully preserved exercise capacity despite the inhibition of NOS.

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Acknowledgements

This work was supported by the European Union from the resources of the European Regional Development Fund under the Innovative Economy Programme (grant coordinated by JCET-UJ, No. POIG.01.01.02-00-069/09). We are grateful to Ms. Krystyna Wandzel for the excellent technical assistance.

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Authors and Affiliations

  1. Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland

    M. Wojewoda, K. Przyborowski, B. Sitek, A. Zakrzewska, L. Mateuszuk & S. Chlopicki

  2. Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Al. Jana Pawla II 78, 31-571, Krakow, Poland

    J. A. Zoladz

  3. Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland

    S. Chlopicki

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  1. M. Wojewoda
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  4. A. Zakrzewska
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Correspondence to S. Chlopicki.

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This work was funded by the European Union from the resources of the European Regional Development Fund under the Innovative Economy Programme (grant coordinated by JCET-UJ, No. POIG.01.01.02-00-069/09).

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Wojewoda, M., Przyborowski, K., Sitek, B. et al. Effects of chronic nitric oxide synthase inhibition on V’O2max and exercise capacity in mice. Naunyn-Schmiedeberg's Arch Pharmacol 390, 235–244 (2017). https://doi.org/10.1007/s00210-016-1318-3

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