Pulsatile stretch induces release of angiotensin II and oxidative stress in human endothelial cells: effects of ACE inhibition and AT1 receptor antagonism

Clin Exp Hypertens. 2008 Oct;30(7):616-27. doi: 10.1080/10641960802443183.

Abstract

Mechanical forces and the activation of the renin-angiotensin system (RAS) may alter the NO/O2(*-) balance, imparing endothelial nitric oxide (NO) availability. This study investigates the link between RAS and NO/O2(*-) balance in human aortic endothelial cells (HAEC) exposed to pulsatile stretch with and without ACE inhibitor quinaprilat or angiotensin II type 1 (AT(1)) receptor antagonist losartan. Pulsatile stretch increased Ang II levels and O2(*-) production, reducing NO release. RAS blockade with quinaprilat or losartan restored the balance between NO and O2(*-). These results provide a molecular basis for understanding the vascular protective effects of ACE inhibition and AT(1) receptor antagonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Biomechanical Phenomena
  • Cells, Cultured
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology*
  • Hemorheology
  • Humans
  • Losartan / pharmacology
  • Models, Biological
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress*
  • Pulsatile Flow
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Stress, Mechanical
  • Superoxides / metabolism
  • Tetrahydroisoquinolines / pharmacology

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Tetrahydroisoquinolines
  • Superoxides
  • Angiotensin II
  • Nitric Oxide
  • quinaprilat
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Losartan