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J Appl Physiol 88: 835-842, 2000;
8750-7587/00 $5.00
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Vol. 88, Issue 3, 835-842, March 2000

Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production

Gregory B. Waypa, Christine A. Morton, Peter A. Vincent, John R. Mahoney Jr., William K. Johnston III, and Fred L. Minnear

Vascular Biology Research Group and Department of Physiology and Cell Biology, Albany Medical College, Albany, New York 12208-3479

The present objective was to determine whether hydrogen peroxide (H2O2) increases transvascular albumin clearance and lung weight in an isolated rat lung and whether posttreatment with cAMP-enhancing agents can prevent these increases. Transvascular albumin clearance was assessed by 125I-labeled albumin clearance (125I-albumin flux/perfusate concentration of 125I-albumin) at a given fluid filtration. Nonlinear regression analysis of transvascular albumin clearance vs. fluid filtration yielded values for the permeability-surface area product (PS) and the reflection coefficient (sigma ). H2O2 decreased sigma  from a control value of 0.93 to 0.38, did not change PS, and increased lung weight. Posttreatment with isoproterenol, a beta 2-adrenergic-receptor agonist, reduced the H2O2-induced decrease in sigma  to 0.65 and augmented the increase in lung weight. Posttreatment with CP-80633, a phosphodiesterase 4 inhibitor, further reduced the H2O2-induced decrease in sigma  to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H2O2 increased PS. Therefore, H2O2 increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H2O2-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.

isoproterenol; phosphodiesterase inhibitor; desferrioxamine; iron chelator; permeability-surface area product; reflection coefficient; vascular pressure; vascular resistance; lung weight


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