9. HMG-COA REDUCTASE INHIBITOR IMPROVES ENDOTHELIAL DYSFUNCTION IN SPONTANEOUS HYPERTENSIVE RATS VIA DOWN-REGULATION OF CAVEOLIN-1 AND ACTIVATION OF ENOS

DOI

10.1016/j.artres.2009.06.021How to use a DOI?

Abstract

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(10mg/kg/day) administered for eight weeks. Abdominal aortic rings were prepared and responses to acetylcholine(10⁻⁹∼10⁻⁴M) 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 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.

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TY  - JOUR
AU  - Dong-Ju Choi
AU  - Eun-Ji Kim
AU  - Min-Jung Park
AU  - Jung-Won Suh
AU  - Hyuk-Jae Chang
AU  - Young-Seok Cho
AU  - Tae-Jin Yeon
AU  - In-Ho Chae
AU  - Kwang-Il Kim
AU  - Cheol-Ho Kim
AU  - Hyo-soo Kim
AU  - Buyng-Hee Oh
AU  - Young-Bae Park
PY  - 2009
DA  - 2009/10/31
TI  - 9. HMG-COA REDUCTASE INHIBITOR IMPROVES ENDOTHELIAL DYSFUNCTION IN SPONTANEOUS HYPERTENSIVE RATS VIA DOWN-REGULATION OF CAVEOLIN-1 AND ACTIVATION OF ENOS
JO  - Artery Research
SP  - 96
EP  - 97
VL  - 3
IS  - 3
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2009.06.021
DO  - 10.1016/j.artres.2009.06.021
ID  - Choi2009
ER  -