Protein kinase inhibitor prevents pulmonary edema in response to H2O2.
We investigated the effect of H2O2 (92 microM) in isolated guinea pig lungs perfused with a buffered Ringer solution. Pulmonary arterial pressure (Ppa), pulmonary capillary pressure (Ppc), and change in lung weight (delta W) were recorded at 0 min and at 15, 30, and 60 min after the H2O2. The capillary filtration coefficient (Kfc) was measured at 0 and 30 min. The perfusion of H2O2 increased the Ppa, Ppc, delta W, and Kfc. The thromboxane synthetase inhibitor Dazoxiben, or the vasodilator papaverine, prevented the increases in Ppa and Ppc. The protein kinase C (PKC) inhibitor H7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride] prevented the increases in Ppa, Ppc, delta W, and Kfc, whereas the inactive isoquinoline HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride] had little effect on the H2O2 response. H2O2 increased the number of stress fibers and disrupted the peripheral band of cultured confluent endothelial cells, changes that were prevented with pretreatment with H7. PKC may mediate the increases in vascular permeability and pulmonary edema that occur in response to H2O2.
Johnson
A
A
Research Service, Veterans Administration Medical Center, Albany, New York.
Phillips
P
P
Hocking
D
D
Tsan
M F
MF
Ferro
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002199:Capillary Permeability; D003599:Cytoskeleton / Q000187:drug effects; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005260:Female; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D011651:Pulmonary Artery / Q000648:ultrastructure; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; D007546:Isoquinolines; D010879:Piperazines; C029166:dazoxiben; D013928:Thromboxane A2; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013930:Thromboxane-A Synthase