Pulsatile stretch induces release of angiotensin II and oxidative stress in human endothelial cells: effects of ACE inhibition and AT1 receptor antagonism.
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.
Delli Gatti
Chiara
C
Cardiovascular Center, University Hospital and Cardiovascular Research, Institute of Physiology, Zurich, Switzerland.
Osto
Elena
E
Kouroedov
Alexei
A
Eto
Masato
M
Shaw
Sidney
S
Volpe
Massimo
M
Lüscher
Thomas F
TF
Cosentino
Francesco
F
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D018056:Hemorheology; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D011673:Pulsatile Flow; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D013481:Superoxides / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044005:Tetrahydroisoquinolines; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; C054501:quinaprilat; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019808:Losartan