Exercise training prevents the inflammatory response to hypoxia in cremaster venules

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas Submitted 6 July 2004 ; accepted in final form 7 February 2005 Systemic hypoxia produces microvascular inflammation in several tissues, including skeletal muscle. Exercise training (ET) has been shown to reduce the inflammatory component of several diseases. Alternatively, ET could influence hypoxia-induced inflammation by improving tissue oxygenation or increasing mechanical antiadhesive forces at the leukocyte-endothelial interface. The effect of 5 wk of treadmill ET on hypoxia-induced microvascular inflammation was studied in the cremaster microcirculation of rats using intravital microscopy. In untrained rats, hypoxia (arterial P O 2 = 32.3 ± 2.1 Torr) increased leukocyte-endothelial adherence from 2.3 ± 0.4 to 10.2 ± 0.3 leukocytes per 100 µm of venule ( P < 0.05) and was accompanied by extravasation of FITC-labeled albumin after 4 h of hypoxia (extra-/intravascular fluorescence intensity ratio = 0.50 ± 0.07). These responses were attenuated in ET (leukocyte adherence was 1.5 ± 0.4 during normoxia and 1.8 ± 0.7 leukocytes per 100 µm venule after 10 min of hypoxia; extra-/intravascular fluorescence intensity ratio = 0.11 ± 0.02; P < 0.05 vs. untrained) despite similar reductions of arterial (32.4 ± 1.8 Torr) and microvascular P O 2 (measured with an oxyphor-quenching method) in both groups. Shear rate decreased during hypoxia to similar extents in ET and untrained rats. In addition, circulating blood leukocyte count was similar in ET and untrained rats. The effects of ET on hypoxia-induced leukocyte-endothelial adherence remained up to 4 wk after discontinuing training. Thus ET attenuated hypoxia-induced inflammation despite similar effects of hypoxia on tissue P O 2 , venular shear rate, and circulating leukocyte count. leukocyte-endothelial adherence; vascular permeability; microvascular P O 2 ; venular shear rate Address for reprint requests and other correspondence: N. C. Gonzalez, Dept. of Molecular and Integrative Physiology, Univ. of Kansas Medical Center, Kansas City, KS 66160 (E-mail: ngonzale{at}kumc.edu )