H2O2 increases sheep tracheal blood flow, permeability, and vascular response to luminal capsaicin

Abstract

Exogenous hydrogen peroxide (H2O2) causes airway epithelial damage in vitro. We have studied the effects of luminal H2O2 in the sheep trachea in vivo on tracheal permeability to low-molecular-weight hydrophilic (technetium-99m-labeled diethylenetriamine pentaacetic acid; 99mTc-DTPA) and lipophilic ([14C]antipyrine; [14C]AP) tracers and on the tracheal vascular response to luminal capsaicin, which stimulates afferent nerve endings. A tracheal artery was perfused, and tracheal venous blood was collected. H2O2 exposure (10 mM) reduced tracheal potential difference (-42.0 +/- 6.4 mV) to zero. It increased arterial and venous flows (56.7 +/- 6.1 and 57.3 +/- 10.0%, respectively; n = 5, P < 0.01, paired t-test) but not tracheal lymph flow (unstimulated flow 5.0 +/- 1.2 microliters.min-1.cm-1, n = 4). During H2O2 exposure, permeability to 99mTc-DTPA increased from -2.6 to -89.7 x 10(-7) cm/s (n = 5, P < 0.05), whereas permeability to [14C]AP (-3,312.6 x 10(-7) cm/s, n = 4) was not altered significantly (-2,565 x 10(-7) cm/s). Luminal capsaicin (10 microM) increased tracheal blood flow (10.1 +/- 4.1%, n = 5) and decreased venous 99mTc-DTPA concentration (-19.7 +/- 4.0, P < 0.01), and these effects were significantly greater after epithelial damage (28.1 +/- 6.0 and -45.7 +/- 4.3%, respectively, P < 0.05, unpaired t-test). Thus H2O2 increases the penetration of a hydrophilic tracer into tracheal blood and lymph but has less effect on a lipophilic tracer. It also enhances the effects of luminal capsaicin on blood flow and tracer uptake.