Yuan Y, Granger H J, Zawieja D C, DeFily D V, Chilian W M
Microcirculation Research Institute, Texas A & M University Health Science Center, College Station 77843-1114.
Am J Physiol. 1993 May;264(5 Pt 2):H1734-9. doi: 10.1152/ajpheart.1993.264.5.H1734.
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.
在本研究中，我们假设小静脉通透性的组胺能增加是由磷脂酶C（PLC）激活触发的级联反应所致，该级联反应诱导一氧化氮（NO）的合成并激活鸟苷酸环化酶。在恒定流量、静水压和胶体渗透压条件下，测量分离的猪冠状动脉小静脉对白蛋白的表观通透系数（Pa）。组胺（2.5、5和10微摩尔）可使Pa短暂且逐渐升高。PLC抑制剂2-硝基-4-羧基苯基N，N-二苯基氨基甲酸酯（NCDC；100微摩尔）可降低基线通透性并消除组胺的作用。NO合酶抑制剂NG-单甲基-L-精氨酸（L-NMMA；10微摩尔）和鸟苷酸环化酶抑制剂6-苯胺基喹啉-5,8-醌（LY 83583；10微摩尔）也可阻断组胺诱导的通透性增加。L-精氨酸（3毫摩尔）可逆转L-NMMA的抑制作用。NG-单甲基-D-精氨酸不影响组胺的作用。此外，硝普钠（10微摩尔）可使Pa增加两到三倍；LY 83583存在时该效应被阻断，但NCDC存在时未改变。结果表明，组胺通过PLC-NO合酶-鸟苷酸环化酶信号级联直接作用于小静脉内皮细胞，从而增加冠状动脉小静脉通透性。
