CHARACTERIZATION AND MECHANISMS OF H2O2-INDUCED CONTRACTIONS OF PULMONARY-ARTERIES

We studied H2O2-induced contractions of isolated rabbit intrapulmonary arteries mounted in standard tissue baths. All vessels were pretreate d with a thromboxane A2/prostaglandin H-2 receptor antagonist, SQ 29,5 48, to block immediate transient contractions to H2O2 and to isolate s lowly developing sustained contractions. When exposed to H2O2 (0.1, 0. 2, 0.3, 0.6, and 1.0 mM) for 30 min, vessels contracted in a concentra tion-dependent fashion between 0.1 and 0.3 mM H2O2; contractions at 0. 6 and 1.0 mM H2O2 were not significantly different from those at 0.3 m M H2O2. During recovery (90 min) from H2O2 exposures, baseline tension was significantly greater, but active tension (10 muM phenylephrine) was significantly less for vessels previously exposed to 0.6 and 1.0 m M H2O2. Contractions to 0.3 mM H2O2 were not blunted by the following interventions: 1) endothelium rubbing, 2) incubation in Ca2+-free 100 AM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic ac id (EGTA) Krebs-Ringer solution, 3) incubation in the Ca2+-free soluti on and depletion of ryanodine (20 muM)-sensitive Ca2+ Stores, or 4) pr etreatment with the protein kinase C inhibitor 1-(5-isoquinolinylsulfo nyl)-3-methyl-piperazine (20 muM). However, contractions were depresse d by approximately 50% when vessels were pretreated with the phospholi pase C/serine esterase inhibitor 2-nitro-4-carboxy-phenyl-N,N-diphenyl carbamate (50 muM). These results suggest that slow-developing contrac tions to H2O2 are concentration dependent and may result, in part, fro m activation of a serine esterase(s) and/or phospholipase C.