title: Immobilization stress induces endothelial dysfunction by oxidative stress via the activation of the angiotensin II/its type I receptor pathway.
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 (AT(1)) receptor signaling pathway.
  
  
  RESULTS
  Rats (n=30) were subjected to immobilization stress (120 min/day) for 14 days using a restrainer. During immobilized period, rats were orally administrated with or without the angiotensin converting enzyme (ACE) inhibitor ramipril (3 mg/kg/day, n=10) or AT(1) receptor inhibitor losartan (9 mg/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 gp91(phox) 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/AT(1) receptor signaling pathway, thereby provoking endothelial dysfunction which can contribute to the development of atherosclerosis and hypertension.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, Republic of Korea. ickmo@ewha.ac.kr
authors.forename: Ick-Mo
authors.initials: IM
authors.lastname: Chung
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Yoo
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Shin
authors.forename: Chun-Ki
authors.initials: CK
authors.lastname: Kim
authors.forename: Suk Hyo
authors.initials: SH
authors.lastname: Suh
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D007103:Immobilization; D019808:Losartan / Q000494:pharmacology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D052250:Nitric Oxide Synthase Type III; D019808:Losartan; D017257:Ramipril; D000109:Acetylcholine