title: 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.
authors.affiliation: Department of Physiology, St. George's Hospital Medical School, London, United Kingdom.
authors.forename: U M
authors.initials: UM
authors.lastname: Wells
authors.forename: S
authors.initials: S
authors.lastname: Duneclift
authors.forename: J G
authors.initials: JG
authors.lastname: Widdicombe
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D014132:Trachea / Q000187:drug effects*
chemical_list: D006861:Hydrogen Peroxide; D002211:Capsaicin