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Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats.
Nephrol Dial Transplant. 2001 Apr; 16(4):746-54.ND

Abstract

BACKGROUND

We documented recently that increased endothelin-1 (ET-1) production in blood vessels and glomeruli of uraemic rats plays a crucial role in the development of hypertension and the progression of chronic renal failure. Normally, biological effects and local production of ET-1 are attenuated by the immediate release of nitric oxide (NO). Increasing evidence suggest, however, that NO release is impaired in chronic renal failure. We investigated whether supplementation with L-arginine, the natural precursor of NO, improves NO synthesis in uraemic rats with reduced renal mass and modulates vascular and renal ET-1 production as well as blood pressure and renal failure progression.

METHODS

One week after surgical renal mass reduction, the uraemic and sham-operated animals received either no treatment or 0.1% L-arginine in drinking water for 5 weeks. In another series of experiments, uraemic rats received 1% L-arginine for 5 weeks. Immunoreactive-ET-1 (ir-ET-1) levels in plasma, urine, and vascular and renal tissue preparations was measured by radioimmunoassay after sample extraction and purification.

RESULTS

Before treatment, systolic blood pressure was significantly elevated in uraemic animals compared to sham-operated controls (156+/-7 vs 111+/-3 mmHg, respectively; P<0.01). Thereafter, systolic blood pressure increased further in uraemic-untreated rats (systolic blood pressure at week 5; 199+/-9 mmHg, P<0.01), whereas it remained similar in uraemic rats supplemented with 0.1% L-arginine (171+/-9 mmHg, NS). At the end of the study, serum creatinine and urea, proteinuria and ir-ET-1 excretion were significantly augmented, while creatinine clearance was reduced in uraemic animals compared to the controls. Ir-ET-1 level was also increased in glomeruli as well as in thoracic aorta, mesenteric arterial bed, and pre-glomerular arteries, and was associated with vascular hypertrophy as assessed by tissue weight. In contrast, ir-ET-1 level was diminished in the renal papilla of uraemic rats. Treatment with 0.1% L-arginine significantly reduced proteinuria and urinary ir-ET-1 excretion (P<0.05) as well as ir-ET-1 level in glomeruli (P<0.01) and in thoracic aorta (P<0.05). These changes were associated with increased plasma NO metabolites NO2/NO3 levels in L-arginine-treated animals (P<0.01) and reduced aortic hypertrophy (P<0.05). In contrast, supplementation with 1% L-arginine had no effect on systolic blood pressure in uraemic rats, but exacerbated proteinuria and urinary ir-ET-1 excretion and increased serum urea (P<0.05) were observed.

CONCLUSIONS

These results indicate that improvement of NO release with a low dose but not with a high dose of L-arginine significantly attenuates the development of hypertension and the progression of renal insufficiency in rats with reduced renal mass. These protective effects may be mediated in part by the reduction of vascular and renal ET-1 production.

Authors+Show Affiliations

Research Center and Division of Nephrology, CHUQ, L'Hôtel-Dieu de Québec, and Department of Medicine, Laval University, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11274268

Citation

Dumont, Y, et al. "Supplementation With a Low Dose of L-arginine Reduces Blood Pressure and Endothelin-1 Production in Hypertensive Uraemic Rats." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 16, no. 4, 2001, pp. 746-54.
Dumont Y, D'Amours M, Lebel M, et al. Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats. Nephrol Dial Transplant. 2001;16(4):746-54.
Dumont, Y., D'Amours, M., Lebel, M., & Larivière, R. (2001). Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 16(4), 746-54.
Dumont Y, et al. Supplementation With a Low Dose of L-arginine Reduces Blood Pressure and Endothelin-1 Production in Hypertensive Uraemic Rats. Nephrol Dial Transplant. 2001;16(4):746-54. PubMed PMID: 11274268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats. AU - Dumont,Y, AU - D'Amours,M, AU - Lebel,M, AU - Larivière,R, PY - 2001/3/29/pubmed PY - 2001/7/6/medline PY - 2001/3/29/entrez SP - 746 EP - 54 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 16 IS - 4 N2 - BACKGROUND: We documented recently that increased endothelin-1 (ET-1) production in blood vessels and glomeruli of uraemic rats plays a crucial role in the development of hypertension and the progression of chronic renal failure. Normally, biological effects and local production of ET-1 are attenuated by the immediate release of nitric oxide (NO). Increasing evidence suggest, however, that NO release is impaired in chronic renal failure. We investigated whether supplementation with L-arginine, the natural precursor of NO, improves NO synthesis in uraemic rats with reduced renal mass and modulates vascular and renal ET-1 production as well as blood pressure and renal failure progression. METHODS: One week after surgical renal mass reduction, the uraemic and sham-operated animals received either no treatment or 0.1% L-arginine in drinking water for 5 weeks. In another series of experiments, uraemic rats received 1% L-arginine for 5 weeks. Immunoreactive-ET-1 (ir-ET-1) levels in plasma, urine, and vascular and renal tissue preparations was measured by radioimmunoassay after sample extraction and purification. RESULTS: Before treatment, systolic blood pressure was significantly elevated in uraemic animals compared to sham-operated controls (156+/-7 vs 111+/-3 mmHg, respectively; P<0.01). Thereafter, systolic blood pressure increased further in uraemic-untreated rats (systolic blood pressure at week 5; 199+/-9 mmHg, P<0.01), whereas it remained similar in uraemic rats supplemented with 0.1% L-arginine (171+/-9 mmHg, NS). At the end of the study, serum creatinine and urea, proteinuria and ir-ET-1 excretion were significantly augmented, while creatinine clearance was reduced in uraemic animals compared to the controls. Ir-ET-1 level was also increased in glomeruli as well as in thoracic aorta, mesenteric arterial bed, and pre-glomerular arteries, and was associated with vascular hypertrophy as assessed by tissue weight. In contrast, ir-ET-1 level was diminished in the renal papilla of uraemic rats. Treatment with 0.1% L-arginine significantly reduced proteinuria and urinary ir-ET-1 excretion (P<0.05) as well as ir-ET-1 level in glomeruli (P<0.01) and in thoracic aorta (P<0.05). These changes were associated with increased plasma NO metabolites NO2/NO3 levels in L-arginine-treated animals (P<0.01) and reduced aortic hypertrophy (P<0.05). In contrast, supplementation with 1% L-arginine had no effect on systolic blood pressure in uraemic rats, but exacerbated proteinuria and urinary ir-ET-1 excretion and increased serum urea (P<0.05) were observed. CONCLUSIONS: These results indicate that improvement of NO release with a low dose but not with a high dose of L-arginine significantly attenuates the development of hypertension and the progression of renal insufficiency in rats with reduced renal mass. These protective effects may be mediated in part by the reduction of vascular and renal ET-1 production. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/11274268/Supplementation_with_a_low_dose_of_L_arginine_reduces_blood_pressure_and_endothelin_1_production_in_hypertensive_uraemic_rats_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/16.4.746 DB - PRIME DP - Unbound Medicine ER -