H 2 o 2 increases sheep tracheal blood flow, permeability and
vascular response to luminal capsaicin.
Widdicombe, U M Wells S Duneclift & J G.
Department of Physiology, St George's Hospital Medical School,
London SW17 ORE, United Kingdom
APStracts 3:0479A, 1996.
Exogenous hydrogen peroxide causes airway epithelial damage in vitro.
We have studied the effects of luminal H2O2 in the sheep trachea in
vivo on tracheal permeability (P) to low MW hydrophilic
(99mtechnetium-labelled diethylene triamine penta acetic 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. 10 mM H2O2 exposure reduced tracheal
potential difference (-42.0+/-6.4 mV) to zero. It increased arterial
and venous flows (Qa: +56.7+/-6.1%, Qv: +57.3+/-10.0%, n=5,
P<0.01, paired t-test) but not tracheal lymph flow
(unstimulated flow: 5.0+/-1.2 [mu]l.min-1.cm-1, n=4). During H2O2
exposure PDTPA increased from -2.6 x 10-7 cm.s-1 to -89.7 x 10-7
cm.s-1 (n=5, P<0.05), whilst PAP (-3312.6 x 10-7 cm.s-1, n=4)
was not altered significantly (-2565 x 10-7 cm.s-1). Luminal
capsaicin (10 [mu]M) 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.
Received 15 April 1996; accepted in final form 24 September 1996.
APS Manuscript Number A353-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996