Effect of chronic tetrahydrobiopterin supplementation on blood pressure and proteinuria in 5/6 nephrectomized rats

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Eduardo PodjarnyJacques Bernheim

Abstract

Tetrahydrobiopterin (BH4) is a key cofactor of nitric oxide (NO) synthase. Reduced BH4 levels may mediate endothelial NO synthase uncoupling, resulting in reduced NO synthesis and enhanced oxidative stress. In rats after 5/6 nephrectomy (Nx), administration of BH4 prevents the onset of hypertension, typically observed 10 days after Nx. This effect is associated with an increased synthesis of NO. The aim of the present study was to evaluate the effect of chronic BH4 therapy on blood pressure and renal morphology. During an 8 week period, five groups of rats were studied: untreated 5/6 Nx rats, BH4-treated Nx rats (BH4, 10 mg/kg body weight/day administered intraperitoneally), l-arginine treated Nx rats (LA, 130 mg/kg/day), diltiazem-treated Nx rats (DILT, 30 mg/kg/day) and sham-operated rats. Treatments were commenced 24 h after surgery. Systolic blood pressure values (SBP), 24 h proteinuria (UP) and creatinine clearance rate (CCR) were assessed before and at weeks 4 and 8 of the study period. Histological changes in the kidney were evaluated at the end of the study (week 8). Compared with baseline, in Nx rats both SBP and UP increased significantly (112+/-1 to 136+/- 1.4 mmHg, P<0.01 and 23+/-2 to 127 +/- 26 mg/day, P<0.01, res...Continue Reading

References

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Citations

Mar 28, 2008·Current Hypertension Reports·Muhiddin A Ozkor, Arshed A Quyyumi
Jun 4, 2011·Cardiology Research and Practice·Christopher R Martens, David G Edwards
Jul 11, 2006·Medical Hypotheses·Mark F McCarty
Jun 13, 2012·Renal Failure·Xiaofang YuXiaoqiang Ding
Feb 27, 2010·American Journal of Hypertension·Mya ThidaYi Zhang
Dec 16, 2006·The Journal of Clinical Hypertension·Matthias HermannThomas F Lüscher
Aug 19, 2007·Clinical Journal of the American Society of Nephrology : CJASN·Sofia B AhmedNorman K Hollenberg
Dec 6, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jeanie ParkArshed A Quyyumi
Jun 2, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Anwar Y DunbarYoichi Osawa
May 4, 2012·American Journal of Physiology. Renal Physiology·Idit F SchwartzDoron Schwartz
Sep 5, 2018·International Journal of Molecular Sciences·Ashfaq AhmadJoseph K Ritter
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natalia A ShnayderRegina F Nasyrova

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