title: Effects of chronic nitric oxide synthase inhibition on V'O2maxand exercise capacity in mice.
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'O2maxand 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'O2maxand 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'O2maxand better running capacity than age-matched control mice. In LN2 mice, NO bioavailability was preserved, as evidenced by maintained NO2-plasma concentration. PGI2production was activated (increased 6-keto-PGF1αplasma 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-PGF1αplasma 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 PGI2and increased number of RBCs, which might explain the fully preserved exercise capacity despite the inhibition of NOS.
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Wojewoda
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Przyborowski
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Sitek
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Zakrzewska
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Mateuszuk
authors.affiliation: Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Al. Jana Pawla II 78, 31-571, Krakow, Poland.
authors.forename: J A
authors.initials: JA
authors.lastname: Zoladz
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348, Krakow, Poland. stefan.chlopicki@jcet.eu.|Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland. stefan.chlopicki@jcet.eu.
authors.forename: S
authors.initials: S
authors.lastname: Chlopicki
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000222:Adaptation, Physiological; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D017079:Exercise Tolerance / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D005082:Physical Exertion; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: Endothelial dysfunction; Exercise capacity; Nitric oxide deficiency; Prostacyclin