HMG-CoA reductase inhibitor improves endothelial dysfunction in spontaneous hypertensive rats via Down-regulation of caveolin-1 and activation of endothelial nitric oxide synthase

Jung Won Suh, Dong Ju Choi, Hyuk Jae Chang, Young Seok Cho, Tae Jin Youn, In Ho Chae, Kwang Il Kim, Cheol Ho Kim, Hyo soo Kim, Buyng Hee Oh, Young Bae Park

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24 Citations (Scopus)

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 (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, phosphorylatedeNOS 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.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalJournal of Korean medical science
Volume25
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1

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Caveolin 1
Nitric Oxide Synthase Type III
Oxidoreductases
Down-Regulation
Nitric Oxide
Acetylcholine
Caveolins
Hypertension
Serine
Aorta
Phosphorylation
3-hydroxy-3-methylglutaryl-coenzyme A
RNA
Control Groups

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Suh, Jung Won ; Choi, Dong Ju ; Chang, Hyuk Jae ; Cho, Young Seok ; Youn, Tae Jin ; Chae, In Ho ; Kim, Kwang Il ; Kim, Cheol Ho ; Kim, Hyo soo ; Oh, Buyng Hee ; Park, Young Bae. / HMG-CoA reductase inhibitor improves endothelial dysfunction in spontaneous hypertensive rats via Down-regulation of caveolin-1 and activation of endothelial nitric oxide synthase. In: Journal of Korean medical science. 2010 ; Vol. 25, No. 1. pp. 16-23.
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HMG-CoA reductase inhibitor improves endothelial dysfunction in spontaneous hypertensive rats via Down-regulation of caveolin-1 and activation of endothelial nitric oxide synthase. / Suh, Jung Won; Choi, Dong Ju; Chang, Hyuk Jae; Cho, Young Seok; Youn, Tae Jin; Chae, In Ho; Kim, Kwang Il; Kim, Cheol Ho; Kim, Hyo soo; Oh, Buyng Hee; Park, Young Bae.

In: Journal of Korean medical science, Vol. 25, No. 1, 01.01.2010, p. 16-23.

Research output: Contribution to journalArticle

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AU - Suh, Jung Won

AU - Choi, Dong Ju

AU - Chang, Hyuk Jae

AU - Cho, Young Seok

AU - Youn, Tae Jin

AU - Chae, In Ho

AU - Kim, Kwang Il

AU - Kim, Cheol Ho

AU - Kim, Hyo soo

AU - Oh, Buyng Hee

AU - Park, Young Bae

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N2 - 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, phosphorylatedeNOS 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.

AB - 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, phosphorylatedeNOS 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.

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