Glomerular thrombosis in pregnancy: role of the L-arginine-nitric oxide pathway.
E. coli endotoxin (LPS) and certain cytokines induce synthesis of nitric oxide (NO) from L-arginine, but also promote endothelial injury and intravascular coagulation. NO has vasodilator and antithrombogenic properties. We investigated the relationship between the L-arginine-NO pathway 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 urinary NO2-/NO3- (end products of NO) increased 200% (P < 0.05), plasma L-arginine did not change, and glomerular thrombosis was minimal. Pregnant rats given 0.75 mg/kg/body wt of LPS developed glomerular thrombosis in 75% of glomeruli (P < 0.05). In these rats plasma L-arginine fell 98%, from 53 +/- 4 to 1.4 +/- 0.9 mmol/liter (P < 0.05) but the urinary NO2-/NO3- did not increase. Oral administration of L-arginine but not D-arginine increased urinary NO2-/NO3- by 250% and averted glomerular 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- concomitantly increased over 200% (P < 0.05). Plasma endothelin-1 increased only in rats exhibiting glomerular thrombosis. Thus, limited maternal reserve capability for NO synthesis may underlie, at least in part, the susceptibility for glomerular thrombosis in pregnancy.
Raij
L
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Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota.
D000818:Animals; D001120:Arginine / Q000097:blood*; D016232:Endothelins / Q000097:blood; D004926:Escherichia coli; D005260:Female; D005920:Glomerular Mesangium / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000652:urine; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000473:pathology / Q000503:physiopathology*
D016232:Endothelins; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine