Reduction in basal nitric oxide activity causes albuminuria

Diabetes. 2011 Feb;60(2):572-6. doi: 10.2337/db09-1630.

Abstract

Objective: The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans.

Research design and methods: To assess the effect of endothelial dysfunction on albuminuria, we measured the urine albumin-to-creatinine ratio (UACR) both before and after the blockade of NO synthases (NOSs) with systemic infusion of N(G)-monomethyl-L-arginine (L-NMMA) in two distinct study populations. In population A, 62 hypertensive patients with type 2 diabetes and, in population B, 22 patients with hypercholesterolemia but without hypertension or type 2 diabetes were examined. All subjects had normal renal function.

Results: There was a significant increase in the UACR in response to NOS inhibition with L-NMMA in hypertensive patients with type 2 diabetes (study population A) and in patients with hypercholesterolemia (study population B). Linear regression analyses revealed that the change in mean arterial presssure in response to L-NMMA was not related to the increase in the UACR in response to L-NMMA in either population, even after adjusting for filtration fraction.

Conclusions: NOS inhibition provokes albuminuria that is unrelated to changes in blood pressure. It is noteworthy that this finding was evident in patient groups prone to endothelial dysfunction and albuminuria. Thus, acute deterioration of endothelial function by reducing NO activity causes an increase in albuminuria.

Trial registration: ClinicalTrials.gov NCT00136188.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albumins
  • Albuminuria / chemically induced
  • Albuminuria / metabolism*
  • Albuminuria / physiopathology
  • Blood Pressure / drug effects
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Humans
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / physiopathology
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Regression Analysis
  • omega-N-Methylarginine / pharmacology

Substances

  • Albumins
  • omega-N-Methylarginine
  • Nitric Oxide
  • Creatinine
  • Nitric Oxide Synthase

Associated data

  • ClinicalTrials.gov/NCT00136188