In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 298, No. 6 ( 2010-06), p. E1131-E1139
Kurzfassung:
l-Arginine can attenuate pulmonary hypertension (PH) by a mechanism that are not fully understood. This study investigated the molecule mechanism of l-arginine attenuating PH. Sprague Dawley rats were treated with monocrotaline (MCT) with or without l-arginine for 3 or 5 wk. Right ventricular systolic pressure (RVSP), right heart hypertrophy, survival rate, pulmonary artery wall thickness, nitric oxide (NO) concentration, and superoxide anion (O 2 ·− ) generation in the lung were measured. Expressions of endothelial nitric oxide synthase (eNOS) and heat shock protein 90 (HSP90), phosphorylation of eNOS at Ser 1177 , and the association of eNOS and HSP90 in the lung were determined by Western blot and immunoprecipitation experiments. MCT increased RVSP, right heart hypertrophy, mortality, pulmonary artery wall thickness, and O 2 ·− generation and decreased eNOS and HSP90 expression and association, phosphorylation of eNOS at Ser 1177 , and NO production. l-Arginine decreased RVSP, right heart hypertrophy, mortality, O 2 ·− generation, and pulmonary artery wall thickness and increased NO production. l-Arginine increased eNOS expression, phosphorylation of eNOS at Ser 1177 , and association of eNOS and HSP90 without significantly altering HSP90 expression. l-Arginine may act through three pathways, providing a substrate for NO generation, preserving eNOS expression/phosphorylation, and maintaining the association of eNOS and HSP90, which allows restoration of eNOS activity and coupling activity, to maintain the balance between NO and O 2 ·− and delay the development of PH.
Materialart:
Online-Ressource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00107.2010
Sprache:
Englisch
Verlag:
American Physiological Society
Publikationsdatum:
2010
ZDB Id:
1477331-4
SSG:
12
