title: Role of the renin-angiotensin system in the systemic microvascular inflammation of alveolar hypoxia.
abstract: Alveolar hypoxia (AH) induces widespread systemic inflammation. Previous studies have shown dissociation between microvascular Po(2) and inflammation. Furthermore, plasma from AH rats (PAHR) induces mast cell (MC) activation, inflammation, and vasoconstriction in normoxic cremasters, while plasma from normoxic rats does not produce these responses. These results suggest that inflammation of AH is triggered by a blood-carried agent. This study investigated the involvement of the renin-angiotensin system (RAS) in the inflammation of AH. Both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (ANG II) receptor blocker (ANG II RB) inhibited the leukocyte-endothelial adherence produced by AH, as well as the inflammation produced by PAHR in normoxic rat cremasters. MC stabilization with cromolyn blocked the effects of PAHR but not those of topical ANG II on normoxic cremasters, suggesting ANG II generation via MC activation by PAHR. This was supported by the observation that ACE inhibition and ANG II RB blocked the leukocyte-endothelial adherence produced by the MC secretagogue compound 48/80. These results suggest that the intermediary agent contained in PAHR activates MC and stimulates the RAS, leading to inflammation, and imply an RAS role in AH-induced inflammation.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. ngonzale@kumc.edu
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Gonzalez
authors.forename: Julie
authors.initials: J
authors.lastname: Allen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Schmidt
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Casillan
authors.forename: Teresa
authors.initials: T
authors.lastname: Orth
authors.forename: John G
authors.initials: JG
authors.lastname: Wood
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000276:immunology*; D008297:Male; D008833:Microcirculation / Q000276:immunology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*