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

Wells, U. M., S. Duneclift, and J. G. Widdicombe.H₂O₂increases sheep tracheal blood flow, permeability, and vascular response to luminal capsaicin. J. Appl.Physiol. 82(2): 621-631, 1997.Exogenous hydrogenperoxide(H₂O₂)causes airway epithelial damage in vitro. We have studied the effectsof luminalH₂O₂in the sheep trachea in vivo on tracheal permeability tolow-molecular-weight hydrophilic (technetium-99m-labeleddiethylenetriamine pentaacetic acid;^99mTc-DTPA) and lipophilic([¹⁴C]antipyrine;[¹⁴C]AP) tracers andon the tracheal vascular response to luminal capsaicin, whichstimulates afferent nerve endings. A tracheal artery was perfused, andtracheal venous blood was collected. H₂O₂exposure (10 mM) reduced tracheal potential difference(42.0 ± 6.4 mV) to zero. It increased arterial andvenous 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 µl ^· min^{1 ·} cm¹,n = 4). DuringH₂O₂exposure, permeability to ^99mTc-DTPA increased from2.6 to 89.7 × 10⁷ cm/s(n = 5, P < 0.05), whereas permeability to[¹⁴C]AP (3,312.6 × 10⁷ cm/s,n = 4) was not altered significantly(2,565 × 10⁷cm/s). Luminal capsaicin (10 µM) increased tracheal blood flow (10.1 ± 4.1%, n = 5)and decreased venous ^99mTc-DTPAconcentration (19.7 ± 4.0, P < 0.01), and these effects weresignificantly greater after epithelial damage (28.1 ± 6.0 and45.7 ± 4.3%, respectively,P < 0.05, unpairedt-test). Thus H₂O₂increases the penetration of a hydrophilic tracer into tracheal bloodand lymph but has less effect on a lipophilic tracer. It also enhancesthe effects of luminal capsaicin on blood flow and tracer uptake.

     

Estimation of thickness of airwaysurface liquid in ferret trachea in vitro

Duneclift, S., U. Wells, and J. Widdicombe. Estimationof thickness of airway surface liquid in ferret trachea in vitro. J. Appl. Physiol. 83(3): 761-767, 1997.The tracheae of ferrets and rabbits were mounted in vitro inorgan baths. While the tracheae were liquid filled, the permeabilitycoefficient ( P) was determined, and then while thetracheae were air filled, the percent clearance for^99mTc-labeleddiethylenetriaminepentaacetic acid (DTPA) was determined. The thicknessof airway surface liquid (ASL) was estimated by three methods.1) The initial concentration of^99mTc-DTPA and the total amount of^99mTc-DTPA (the sum of thatentering the outside medium, that draining from the trachea, and thatwashed out at the end of 40 min) gave the initial volume of ASL andthus its thickness. Mean values were 45.7 µm for the ferret and 41.9 µm for the rabbit. 2) Estimates ofASL thickness at the end of the 40-min period, based on the final^99mTc-DTPA concentration and theamount in the washout, were 42.9 µm for ferret and 45.4 µm forrabbit. 3) The ratio of Pto percent clearance gave mean ASL thickness values of 49.2 µm forthe ferret and 40.3 µm for the rabbit. Thus three separate methodsfor determining ASL thickness give very similar results, with means inthe range 40-49 µm. Administration of methacholine or atropineto ferret tracheae did not significantly change ASL thickness.