Houssière, Anne, Boutaina Najem, Nicolas Cuylits, Sophie Cuypers, Robert Naeije, and Philippe van de Borne. Hyperoxia enhances metaboreflex sensitivity during static exercise in humans. Am J Physiol Heart Circ Physiol 291: H210 -H215, 2006; doi:10.1152/ajpheart.01168.2005.-Peripheral chemoreflex inhibition with hyperoxia decreases sympathetic nerve traffic to muscle circulation [muscle sympathetic nerve activity (MSNA)]. Hyperoxia also decreases lactate production during exercise. However, hyperoxia markedly increases the activation of sensory endings in skeletal muscle in animal studies. We tested the hypothesis that hyperoxia increases the MSNA and mean blood pressure (MBP) responses to isometric exercise. The effects of breathing 21% and 100% oxygen at rest and during isometric handgrip at 30% of maximal voluntary contraction on MSNA, heart rate (HR), MBP, blood lactate (BL), and arterial O 2 saturation (SaO 2 ) were determined in 12 healthy men. The isometric handgrips were followed by 3 min of postexercise circulatory arrest (PE-CA) to allow metaboreflex activation in the absence of other reflex mechanisms. Hyperoxia lowered resting MSNA, HR, MBP, and BL but increased Sa O 2 compared with normoxia (all P Ͻ 0.05). MSNA and MBP increased more when exercise was performed in hyperoxia than in normoxia (MSNA: hyperoxic exercise, 255 Ϯ 100% vs. normoxic exercise, 211 Ϯ 80%, P ϭ 0.04; and MBP: hyperoxic exercise, 33 Ϯ 9 mmHg vs. normoxic exercise, 26 Ϯ 10 mmHg, P ϭ 0.03). During PE-CA, MSNA and MBP remained elevated (both P Ͻ 0.05) and to a larger extent during hyperoxia than normoxia (P Ͻ 0.05). Hyperoxia enhances the sympathetic and blood pressure (BP) reactivity to metaboreflex activation. This is due to an increase in metaboreflex sensitivity by hyperoxia that overrules the sympathoinhibitory and BP lowering effects of chemoreflex inhibition. This occurs despite a reduced lactic acid production.handgrip; muscle sympathetic nerve activity; metaboreceptors; chemoreceptors MUSCLE METABORECEPTORS regulate sympathetic activation during exercise (19,25). This reflex is activated by metabolites released from exercising skeletal muscle. Several substances, such as lactic acid, phosphate, K ϩ , H ϩ , adenosine, prostaglandins, and bradykinin, are now identified as stimulators of this pressor reflex (35,37,40).These metabolites stimulate group III and IV chemosensitive afferents in the working muscles (32). These afferent fibers can also be activated by injection of lactic acid or a hyperosmolar solution of potassium chloride, and their activity is modulated by endogenous nitric oxide in resting and contracting muscle (3,6,11,13,16). This activation in both nonexercising and exercising limbs (32) provokes a rise in cardiac output and vasoconstriction of the nonischemic vascular beds. As a result, blood pressure (BP) and perfusion pressure increase and correct blood flow deficits during exercise (32,35,40,43).There are several reasons to believe that hyperoxia may affect sympathetic regulation during exercise.First, hyp...