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Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with

Minoru Satoh1, Sohachi Fujimoto, Sayaka Arakawa

  • 1Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan. msatoh@med.kawasaki-m.ac.jp

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|July 4, 2008
PubMed
Abstract

Insights

Angiotensin II receptor blockers (ARBs) improve nitric oxide (NO) and reactive oxygen species (ROS) balance in diabetic nephropathy by increasing tetrahydrobiopterin (BH4) bioavailability, thereby improving endothelial NO synthase (eNOS) uncoupling.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetic nephropathy is linked to an imbalance of nitric oxide (NO) and reactive oxygen species (ROS).
  • Endothelial NO synthase (eNOS) uncoupling contributes to renal dysfunction in diabetic nephropathy.
  • Angiotensin II type 1 receptor blockers (ARBs) show potential in slowing chronic renal disease progression in type 2 diabetes.

Purpose of the Study:

  • To investigate the effects of ARB (losartan) on eNOS uncoupling in a rat model of diabetic nephropathy.
  • To determine if ARB treatment can restore the balance between NO and ROS in diabetic kidneys.

Main Methods:

  • Diabetes was induced in rats using streptozotocin.
  • Rats were treated with saline or losartan (ARB) for two weeks.
  • Glomerular ROS production, NO bioavailability, eNOS dimerization, and tetrahydrobiopterin (BH4) levels were assessed.

Main Results:

  • Losartan significantly reduced glomerular ROS production in diabetic rats.
  • NOS uncoupling, characterized by increased ROS and diminished NO, was observed in diabetic glomeruli.
  • Losartan treatment increased BH4 bioavailability, reversed decreased GTPCH1 expression, and restored eNOS dimerization and NO production.

Conclusions:

  • ARB treatment, specifically losartan, effectively improves eNOS uncoupling in diabetic nephropathy.
  • The mechanism involves enhancing BH4 bioavailability, which restores NO production and reduces oxidative stress.

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