The role of nitric oxide (NO) as a regulator of vasomotor tone has been investigated in resting and exercising human skeletal muscle. At rest, NO synthase (NOS) inhibition by intra-arterial infusion of N^G-monomethyl-L-arginine decreased femoral artery blood flow (FABF, ultrasound Doppler) from 0.39 ± 0.08 to 0.18 ± 0.03 l/min (P < 0.01), i.e., by ~52%, and increased leg O₂ extraction from 62.1 ± 9.8 to 100.9 ± 4.5 ml/l (P < 0.004); thus leg O₂ uptake (O₂, 22 ± 4 ml/min, ~0.75 ml · min¹ · 100 g¹) was unaltered [not significant (P = NS)]. Mean arterial pressure (MAP) increased by 8 ± 2 mmHg (P < 0.01). Heart rate (HR, 53 ± 3 beats/min) was unaltered (P = NS). The NOS inhibition had, however, no effect on the initial rate of rise or the magnitude of FABF (4.8 ± 0.4 l/min, ~163 ml · min¹ · 100 g¹), MAP (117 ± 3 mmHg), HR (98 ± 5 beats/min), or leg O₂ (704 ± 55 ml/min, ~24 ml · min¹ · 100 g¹, P = NS) during submaximal, one-legged, dynamic knee-extensor exercise. Similarly, FABF (7.6 ± 1.0 l/min, ~258 ml · min¹ · 100 g¹), MAP (140 ± 8 mmHg), and leg O₂ (1,173 ± 139 ml/min, ~40 ml · min¹ · 100 g¹) were unaffected at termination of peak effort (P = NS). Peak HR (137 ± 3 beats/min) was, however, lowered by 10% (P < 0.01). During recovery, NOS inhibition reduced FABF by ~34% (P < 0.04), which was compensated for by an increase in the leg O₂ extraction by ~41% (P < 0.04); thus leg O₂ was unaltered (P = NS). In conclusion, these findings indicate that NO is not essential for the initiation or maintenance of active hyperemia in human skeletal muscle but support a role for NO during rest, including recovery from exercise. Moreover, changes in blood flow during rest and recovery caused by NOS inhibition are accompanied by reciprocal changes in O₂ extraction, and thus O₂ is maintained.

blood flow; circulation; exercise; metabolism; vasodilatation

This article has been cited by other articles:

				D. W. Trott, F. Gunduz, M. H. Laughlin, and C. R. Woodman Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries J Appl Physiol, June 1, 2009; 106(6): 1925 - 1934. [Abstract] [Full Text] [PDF]

				S. P. Mortensen, J. Gonzalez-Alonso, L. T. Bune, B. Saltin, H. Pilegaard, and Y. Hellsten ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1140 - R1148. [Abstract] [Full Text] [PDF]

				C. J. Ray and J. M. Marshall Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb J. Physiol., April 1, 2009; 587(7): 1579 - 1591. [Abstract] [Full Text] [PDF]

				H. Komine, K. Matsukawa, H. Tsuchimochi, T. Nakamoto, and J. Murata Sympathetic cholinergic nerve contributes to increased muscle blood flow at the onset of voluntary static exercise in conscious cats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1251 - R1262. [Abstract] [Full Text] [PDF]

				K. L. Jablonski, D. R. Seals, I. Eskurza, K. D. Monahan, and A. J. Donato High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men J Appl Physiol, November 1, 2007; 103(5): 1715 - 1721. [Abstract] [Full Text] [PDF]

				M. J. Joyner and B. W. Wilkins Exercise hyperaemia: is anything obligatory but the hyperaemia? J. Physiol., September 15, 2007; 583(3): 855 - 860. [Abstract] [Full Text] [PDF]

				B. Saltin Exercise hyperaemia: magnitude and aspects on regulation in humans J. Physiol., September 15, 2007; 583(3): 819 - 823. [Abstract] [Full Text] [PDF]

				S. P. Mortensen, J. Gonzalez-Alonso, R. Damsgaard, B. Saltin, and Y. Hellsten Inhibition of nitric oxide and prostaglandins, but not endothelial-derived hyperpolarizing factors, reduces blood flow and aerobic energy turnover in the exercising human leg J. Physiol., June 1, 2007; 581(2): 853 - 861. [Abstract] [Full Text] [PDF]

				W. G. Schrage, J. H. Eisenach, and M. J. Joyner Ageing reduces nitric-oxide- and prostaglandin-mediated vasodilatation in exercising humans J. Physiol., February 15, 2007; 579(1): 227 - 236. [Abstract] [Full Text] [PDF]

				K. K. Kalliokoski, H. Langberg, A. K. Ryberg, C. Scheede-Bergdahl, S. Doessing, A. Kjaer, M. Kjaer, and R. Boushel Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R803 - R809. [Abstract] [Full Text] [PDF]

				E. A. Martin, W. T. Nicholson, J. H. Eisenach, N. Charkoudian, and M. J. Joyner Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia J Appl Physiol, August 1, 2006; 101(2): 492 - 499. [Abstract] [Full Text] [PDF]

				G. K. McConell, N. N. Huynh, R. S. Lee-Young, B. J. Canny, and G. D. Wadley L-Arginine infusion increases glucose clearance during prolonged exercise in humans Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E60 - E66. [Abstract] [Full Text] [PDF]

				L. H. Naylor, C. J. Weisbrod, G. O'Driscoll, and D. J. Green Measuring peripheral resistance and conduit arterial structure in humans using Doppler ultrasound J Appl Physiol, June 1, 2005; 98(6): 2311 - 2315. [Abstract] [Full Text] [PDF]

				J. Sugawara, S. Maeda, T. Otsuki, T. Tanabe, R. Ajisaka, and M. Matsuda Effects of nitric oxide synthase inhibitor on decrease in peripheral arterial stiffness with acute low-intensity aerobic exercise Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2666 - H2669. [Abstract] [Full Text] [PDF]

				J. Rogers and D. D. Sheriff Role of estrogen in nitric oxide- and prostaglandin-dependent modulation of vascular conductance during treadmill locomotion in rats J Appl Physiol, August 1, 2004; 97(2): 756 - 763. [Abstract] [Full Text] [PDF]

				P. S. Clifford and Y. Hellsten Vasodilatory mechanisms in contracting skeletal muscle J Appl Physiol, July 1, 2004; 97(1): 393 - 403. [Abstract] [Full Text] [PDF]

				A. M. Jones, D. P. Wilkerson, S. Wilmshurst, and I. T. Campbell Influence of L-NAME on pulmonary O2 uptake kinetics during heavy-intensity cycle exercise J Appl Physiol, March 1, 2004; 96(3): 1033 - 1038. [Abstract] [Full Text] [PDF]

				D. Merkus, B. Houweling, A. Zarbanoui, and D. J. Duncker Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1114 - H1123. [Abstract] [Full Text] [PDF]

				O. K. Baskurt, O. Yalcin, S. Ozdem, J. K. Armstrong, and H. J. Meiselman Modulation of endothelial nitric oxide synthase expression by red blood cell aggregation Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H222 - H229. [Abstract] [Full Text] [PDF]

				J. L. Olive, J. M. Slade, G. A. Dudley, and K. K. McCully Blood flow and muscle fatigue in SCI individuals during electrical stimulation J Appl Physiol, February 1, 2003; 94(2): 701 - 708. [Abstract] [Full Text] [PDF]

				D. Green, C. Cheetham, C. Reed, L. Dembo, and G. O'Driscoll Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry J Appl Physiol, July 1, 2002; 93(1): 361 - 368. [Abstract] [Full Text] [PDF]

				D. B. Haitsma, D. Merkus, J. Vermeulen, P. D. Verdouw, and D. J. Duncker Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2198 - H2209. [Abstract] [Full Text] [PDF]

				C. L. Murrant and I. H. Sarelius Multiple dilator pathways in skeletal muscle contraction-induced arteriolar dilations Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R969 - R978. [Abstract] [Full Text] [PDF]

				L.-E. Chen, K. Liu, W.-N. Qi, E. Joneschild, X. Tan, A. V. Seaber, J. S. Stamler, and J. R. Urbaniak Role of nitric oxide in vasodilation in upstream muscle during intermittent pneumatic compression J Appl Physiol, February 1, 2002; 92(2): 559 - 566. [Abstract] [Full Text] [PDF]

				M. J. Joyner, N. M. Dietz, and J. T. Shepherd From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs J Appl Physiol, December 1, 2001; 91(6): 2431 - 2441. [Abstract] [Full Text] [PDF]

				C. A. Kindig, P. McDonough, H. H. Erickson, and D. C. Poole Effect of L-NAME on oxygen uptake kinetics during heavy-intensity exercise in the horse J Appl Physiol, August 1, 2001; 91(2): 891 - 896. [Abstract] [Full Text] [PDF]

				Z.-P. Chen, G. K. McConell, B. J. Michell, R. J. Snow, B. J. Canny, and B. E. Kemp AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1202 - E1206. [Abstract] [Full Text] [PDF]

				U. Frandsen, L. Hoffner, A. Betak, B. Saltin, J. Bangsbo, and Y. Hellsten Endurance training does not alter the level of neuronal nitric oxide synthase in human skeletal muscle J Appl Physiol, September 1, 2000; 89(3): 1033 - 1038. [Abstract] [Full Text] [PDF]

				B. A. KINGWELL Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease FASEB J, September 1, 2000; 14(12): 1685 - 1696. [Abstract] [Full Text]

				D. B. Haitsma, D. Merkus, J. Vermeulen, P. D. Verdouw, and D. J. Duncker Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2198 - H2209. [Abstract] [Full Text] [PDF]