Histamine increases venular permeability via a phospholipase C-NO synthase-guanylate cyclase cascade.
In this study, we hypothesized that histaminergic increases in venular permeability result from a cascade triggered by activation of phospholipase C (PLC), inducing the synthesis of nitric oxide (NO) and activating guanylate cyclase. The apparent permeability coefficient to albumin (Pa) was measured in isolated porcine coronary venules subjected to constant flow and hydrostatic and oncotic pressures. Histamine (2.5, 5, and 10 microM) transiently and progressively increased Pa. The PLC inhibitor 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC; 100 microM) decreased baseline permeability and abolished the effect of histamine. The NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10 microM) and the guanylate cyclase inhibitor 6-anilinoquinoline-5,8-quinone (LY 83583; 10 microM) also blocked the histamine-induced hyperpermeability. L-Arginine (3 mM) reversed the inhibition by L-NMMA. NG-monomethyl-D-arginine did not influence the effect of histamine. Furthermore, sodium nitroprusside (10 microM) augmented Pa by two- to threefold; this effect was blocked in the presence of LY 83583 but not altered in the presence of NCDC. The results suggest that histamine increases coronary venular permeability by a direct action on the venular endothelial cells through a PLC-NO synthase-guanylate cyclase-signaling cascade.
Yuan
Y
Y
Microcirculation Research Institute, Texas A & M University Health Science Center, College Station 77843-1114.
Granger
H J
HJ
Zawieja
D C
DC
DeFily
D V
DV
Chilian
W M
WM
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D013552:Swine; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014699:Venules / Q000187:drug effects*
D009569:Nitric Oxide; D006632:Histamine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010738:Type C Phospholipases; D006162:Guanylate Cyclase