L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat

G. D. Helmbrecht, M. Y. Farhat, L. Lochbaum, Heidi E Brown, K. T. Yadgarova, G. S. Eglinton, P. W. Ramwell

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: Inhibition of nitric oxide synthase with Nω-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. STUDY DESIGN: 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.

Original languageEnglish (US)
Pages (from-to)800-805
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume175
Issue number4 I
DOIs
StatePublished - 1996
Externally publishedYes

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NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Arginine
Proteinuria
Blood Pressure
Pregnancy
Pre-Eclampsia
Kidney
Sodium Chloride
Hypertension
Weights and Measures
Nitric Oxide Donors
Growth
Nitrites
Nitrates
Sprague Dawley Rats
Tail
Analysis of Variance
Nitric Oxide
Urine

Keywords

  • L-arginine
  • Nω-nitro-L-arginine methyl ester
  • Preeclampsia
  • rat

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat. / Helmbrecht, G. D.; Farhat, M. Y.; Lochbaum, L.; Brown, Heidi E; Yadgarova, K. T.; Eglinton, G. S.; Ramwell, P. W.

In: American Journal of Obstetrics and Gynecology, Vol. 175, No. 4 I, 1996, p. 800-805.

Research output: Contribution to journalArticle

Helmbrecht, G. D. ; Farhat, M. Y. ; Lochbaum, L. ; Brown, Heidi E ; Yadgarova, K. T. ; Eglinton, G. S. ; Ramwell, P. W. / L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat. In: American Journal of Obstetrics and Gynecology. 1996 ; Vol. 175, No. 4 I. pp. 800-805.
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abstract = "OBJECTIVE: Inhibition of nitric oxide synthase with Nω-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. STUDY DESIGN: 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.",
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AU - Helmbrecht, G. D.

AU - Farhat, M. Y.

AU - Lochbaum, L.

AU - Brown, Heidi E

AU - Yadgarova, K. T.

AU - Eglinton, G. S.

AU - Ramwell, P. W.

PY - 1996

Y1 - 1996

N2 - OBJECTIVE: Inhibition of nitric oxide synthase with Nω-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. STUDY DESIGN: 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.

AB - OBJECTIVE: Inhibition of nitric oxide synthase with Nω-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. STUDY DESIGN: 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.

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