GLOMERULAR THROMBOSIS IN PREGNANCY - ROLE OF THE L-ARGININE-NITRIC OXIDE PATHWAY

E. coli endotoxin (LPS) and certain cytokines induce synthesis of nitr ic oxide (NO) from L-arginine, but also promote endothelial injury and intravascular coagulation. NO has vasodilator and antithrombogenic pr operties. We investigated the relationship between the L-arginine-NO p athway and the susceptibility to LPS-induced glomerular thrombosis in pregnancy. Pregnant rats were given either 0.15 or 0.75 mg/kg/body wt of LPS intraperitoneally. In rats given 0.15 mg/kg/body wt of LPS urin ary NO2-/NO3- (end products of NO) increased 200% (P < 0.05), plasma L -arginine did not change, and glomerular thrombosis was minimal. Pregn ant rats given 0.75 mg/kg/ body wt of LPS developed glomerular thrombo sis in 75% of glomeruli (P < 0.05). In these rats plasma L-arginine fe ll 98%, from 53 +/- 4 to 1.4 +/- 0.9 mmol/liter (P < 0.05) but the uri nary NO2-/NO3- did not increase. Oral administration of L-arginine but not D-arginine increased urinary NO2-/NO3- by 250% and averted glomer ular thrombosis in these rats (P < 0.05). Virgin rats given 0.75 mg/kg /body wt of LPS did not contract glomerular thrombosis. In these rats plasma L-arginine decreased only 40% while urinary NO2-/NO3- concomita ntly increased over 200% (P < 0.05). Plasma endothelin-l increased onl y in rats exhibiting glomerular thrombosis. Thus, limited maternal res erve capability for NO synthesis may underlie, at least in part, the s usceptibility for glomerular thrombosis in pregnancy.