Effects of chronic nitric oxide synthase inhibition on V’O_2max and exercise capacity in mice

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• 作者：M. Wojewoda ; K. Przyborowski ; B. Sitek…
• 关键词：Exercise capacity ; Endothelial dysfunction ; Nitric oxide deficiency ; Prostacyclin
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：390
• 期：3
• 页码：235-244
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Pharmacology/Toxicology; Neurosciences;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1912
• 卷排序：390

文摘

Acute inhibition of NOS by L-NAME (Nω-nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V’O_2max) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V’O_2max 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_2max 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’O_2max 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-PGF_1α 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-PGF_1α 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_2max. 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.