title: Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production.
abstract: The present objective was to determine whether hydrogen peroxide (H(2)O(2)) 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 (125)I-labeled albumin clearance ((125)I-albumin flux/perfusate concentration of (125)I-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). H(2)O(2) 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 H(2)O(2)-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 H(2)O(2)-induced decrease in sigma to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H(2)O(2) increased PS. Therefore, H(2)O(2) increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H(2)O(2)-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.
authors.affiliation: Vascular Biology Research Group and Department of Physiology and Cell Biology, Albany Medical College, Albany, New York 12208-3479, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Waypa
authors.forename: C A
authors.initials: CA
authors.lastname: Morton
authors.forename: P A
authors.initials: PA
authors.lastname: Vincent
authors.forename: J R
authors.initials: JR
authors.lastname: Mahoney
authors.forename: W K
authors.initials: WK
authors.lastname: Johnston
authors.forename: F L
authors.initials: FL
authors.lastname: Minnear
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; C101589:CP 80633; D002614:Chelating Agents; D010726:Phosphodiesterase Inhibitors; D011744:Pyrimidinones; D012710:Serum Albumin, Bovine; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D003676:Deferoxamine; D007545:Isoproterenol