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Article de Anglais | WPRIM | ID: wpr-225001

RÉSUMÉ

Hypertension is associated with endothelial dysfunction and increased cardiovascular risk. Caveolin-1 regulates nitric oxide (NO) signaling by modulating endothelial nitric oxide synthase (eNOS). The purpose of this study was to examine whether HMG-CoA reductase inhibitor improves impaired endothelial function of the aorta in spontaneous hypertensive rat (SHR) and to determine the underlying mechanisms involved. Eight-week-old male SHR were assigned to either a control group (CON, n=11) or a rosuvastatin group (ROS, n=12), rosuvastatin (10 mg/kg/day) administered for eight weeks. Abdominal aortic rings were prepared and responses to acetylcholine (10-9-10-4 M) were determined in vitro. To evaluate the potential role of NO and caveolin-1, we examined the plasma activity of NOx, eNOS, phosphorylated-eNOS and expression of caveolin-1. The relaxation in response to acetylcholine was significantly enhanced in ROS compared to CON. Expression of eNOS RNA was unchanged, whereas NOx level and phosphorylated-eNOS at serine-1177 was increased accompanied with depressed level of caveolin-1 in ROS. We conclude that 3-Hydroxy-3-methylglutaryl Coenzyme-A (HMG-CoA) reductase inhibitor can improve impaired endothelial dysfunction in SHR, and its underlying mechanisms are associated with increased NO production. Furthermore, HMG-CoA reductase inhibitor can activate the eNOS by phosphorylation related to decreased caveolin-1 abundance. These results imply the therapeutic strategies for the high blood pressure-associated endothelial dysfunction through modifying caveolin status.


Sujet(s)
Animaux , Mâle , Rats , Acétylcholine/métabolisme , Aorte/métabolisme , Pression sanguine/effets des médicaments et des substances chimiques , Cavéoline-1/métabolisme , Régulation négative , Calendrier d'administration des médicaments , Endothélium vasculaire/effets des médicaments et des substances chimiques , Fluorobenzènes/administration et posologie , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/administration et posologie , Hypertension artérielle/enzymologie , Monoxyde d'azote/sang , Nitric oxide synthase type III/métabolisme , Phosphorylation , Pyrimidines/administration et posologie , Rats de lignée SHR , Sulfonamides/administration et posologie , Vasodilatation/effets des médicaments et des substances chimiques
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