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-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome of hypertension, proteinuria, intrauterine growth restriction, and renal glomerular capillary endothelial lesions in pregnant rats. We attempted to reverse these changes with late-pregnancy administration of L-arginine.


METHODS
Sprague Dawley rats with timed pregnancies received 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 term. 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 via tail cuff on days 10, 16, and 21. Pup weights were assessed at delivery, serum and urine were collected and analyzed for nitrites and nitrates, and renal tissue was processed for histologic examination. Data were analyzed with the one-way analysis of variance and the Newman-Keuls test for multiple comparisons.


RESULTS
In the L-NAME-treated animals L-arginine significantly lowered systolic blood pressure at late pregnancy (125 +/- 2.42 vs 153 +/- 3.0 mm Hg) (p < 0.01), increased mean 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), and decreased the proportion of injured glomeruli (7% vs 64%) (p < 0.001).


CONCLUSIONS
Lesions induced by chronic inhibition of endothelium-derived nitric oxide synthesis (hypertension, intrauterine growth restriction, proteinuria, renal glomerulus injury) are reversed by treatment with L-arginine. These findings lend support to the potential for use of nitric oxide donors in the treatment and prevention of preeclampsia.
Helmbrecht
G D
GD
Department of Obstetrics and Gynecology, Georgetown University Medical School, Washington, DC 20007, USA.
Farhat
M Y
MY
Lochbaum
L
L
Brown
H E
HE
Yadgarova
K T
KT
Eglinton
G S
GS
Ramwell
P W
PW
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011225:Pre-Eclampsia / Q000139:chemically induced*; D011247:Pregnancy; D011507:Proteinuria / Q000652:urine; D051381:Rats
D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester