L-ARGININE REVERSES THE ADVERSE PREGNANCY CHANGES INDUCED BY NITRIC-OXIDE SYNTHASE INHIBITION IN THE RAT

OBJECTIVE: Inhibition of nitric oxide synthase with N omega-nitro-L-ar ginine methyl ester (L-NAME) induces a preeclampsia-like syndrome of h ypertension, proteinuria, intrauterine growth restriction, and renal g lomerular capillary endothelial lesions in pregnant rats. We attempted to reverse these changes with late-pregnancy administration of L-argi nine. STUDY DESIGN: Sprague Dawley rats with timed pregnancies receive d infusions of either saline solution (n = 12) (group SC) or L-NAME (n = 12) (group LC) (160 mg/kg per day) on gestational day 10 through te rm. On gestational day 16 half of the saline solution group (group SA) and half of the L-NAME group (group LA) received L-arginine (21 mg/kg per day) through delivery, Systolic blood pressures were determined v ia tail cuff on days 10, 16, and 21. Pup weights were assessed at deli very, serum and urine were collected and analyzed for nitrites and nit rates, and renal tissue was processed for histologic examination. Data were analyzed with the one-way analysis of variance and the Newman-Ke uls test for multiple comparisons. RESULTS: In the L-NAME-treated anim als L-arginine significantly lowered systolic blood pressure at late p regnancy (125 +/- 2.42 vs 153 +/- 3.0 mm Hg) (p < 0.01), increased mea n pup weight (5.6 +/- 0.11 gm in group LA vs 5.0 +/- 0.02 gm in group LC) (p < 0.001), decreased the degree of proteinuria (2+ vs trace), an d decreased the proportion of injured glomeruli (7% vs 64%) (p < 0.001 ). CONCLUSIONS: Lesions induced by chronic inhibition of endothelium-d erived nitric oxide synthesis (hypertension, intrauterine growth restr iction, proteinuria, renal glomerulus injury) are reversed by treatmen t with L-arginine. These findings (end support to the potential for us e of nitric oxide donors in the treatment and prevention of preeclamps ia.