We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

No abstract

SummaryActivation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.

No abstract

No abstract