Immobilization stress induces endothelial dysfunction by oxidative stress via the activation of the angiotensin II/its type I receptor pathway

Ick Mo Chung, Young Myeong Kim, Mi Hyun Yoo, Mi Kyung Shin, Chun Ki Kim, Suk Hyo Suh

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Objective: Psychological stress has been shown to contribute to the development of atherosclerosis; however its underlying mechanism has not been clearly elucidated. We here studied the mechanism by which immobilization stress causes endothelial dysfunction with specific aim of identifying the role of angiotensin II and its type I (AT1) receptor signaling pathway. Methods and results: Rats (n=30) were subjected to immobilization stress (120min/day) for 14 days using a restrainer. During immobilized period, rats were orally administrated with or without the angiotensin converting enzyme (ACE) inhibitor ramipril (3mg/kg/day, n=10) or AT1 receptor inhibitor losartan (9mg/kg/day, n=10). Immobilization significantly increased systolic blood pressure and decreased acetylcholine-induced ex vivo relaxation of arteries compared with those of control animals (n=10). Immobilization increased the plasma levels of angiotensin II and ACE activity that were inhibited by treatment with ramipril, but not losartan. Furthermore, immobilization increased the plasma level of malondialdehyde and expression of gp91phox and Rho-associated kinase-1 in arteries, and decreased the arterial eNOS mRNA and oxidized products of NO (nitrite plus nitrate). These functional and biochemical alterations induced by immobilization were significantly reversed by administration of ramipril or losartan. Conclusions: Immobilization stress induces vascular oxidative stress by activating the angiotensin II/AT1 receptor signaling pathway, thereby provoking endothelial dysfunction which can contribute to the development of atherosclerosis and hypertension.

Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalAtherosclerosis
Volume213
Issue number1
DOIs
StatePublished - Nov 2010

Keywords

  • Angiotensin II
  • Endothelial function
  • Hypertension
  • Nitric oxide
  • Oxidative stress
  • Psychological stress

Fingerprint

Dive into the research topics of 'Immobilization stress induces endothelial dysfunction by oxidative stress via the activation of the angiotensin II/its type I receptor pathway'. Together they form a unique fingerprint.

Cite this