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Long-Term Angiotensin II Receptor Blockade Limits Hypertension, Aortic Dysfunction, and Structural Remodeling in a

Omar Z Ameer1, Mark Butlin, Elena Kaschina

  • 1Department of Biomedical Science, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

Journal of Vascular Research
|November 24, 2016
PubMed

Insights

Valsartan treatment improved aortic function and structure in rats with chronic kidney disease (CKD). This study shows angiotensin II (Ang II) drives vascular damage in CKD, and early intervention limits these pathological changes.

Area of Science:

  • Cardiovascular Research
  • Nephrology
  • Pharmacology

Background:

  • Chronic kidney disease (CKD) is linked to significant large artery remodeling, endothelial dysfunction, and calcification.
  • Angiotensin II (Ang II) is a key mediator in the vascular pathologies associated with CKD.

Purpose of the Study:

  • To investigate the long-term effects of angiotensin II type 1 receptor inhibition with valsartan on aortic function and structure in a rat model of CKD.
  • To assess valsartan's impact on vascular remodeling, endothelial function, and calcification in the context of chronic kidney disease.

Main Methods:

  • Lewis polycystic kidney (LPK) rats and Lewis control rats were treated with valsartan (60 mg/kg/day) or vehicle from 4 to 18 weeks.
  • In vitro functional assessments included responses to noradrenaline, potassium chloride, and relaxations to acetylcholine (ACh) and sodium nitroprusside (SNP).
  • The roles of nitric oxide synthase (NOS) and cyclooxygenase pathways were examined using L-arginine, L-NAME, and indomethacin.

Main Results:

  • Valsartan significantly reduced systolic blood pressure and urinary protein in LPK rats.
  • Treatment normalized endothelium-dependent and independent relaxations and improved nitric oxide-dependent relaxation.
  • Valsartan decreased aortic wall hypertrophy, elastin fragmentation, calcification, and matrix metalloproteinase 9 levels.

Conclusions:

  • Angiotensin II plays a critical role in the vascular manifestations of chronic kidney disease.
  • Early therapeutic intervention with valsartan can substantially mitigate the pathological vascular changes associated with CKD.
Abstract

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