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 language | English |
|---|---|
| Pages (from-to) | 16-23 |
| Number of pages | 8 |
| Journal | Journal of Korean medical science |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Medicine(all)
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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 journal › Article
TY - JOUR
T1 - HMG-CoA reductase inhibitor improves endothelial dysfunction in spontaneous hypertensive rats via Down-regulation of caveolin-1 and activation of endothelial nitric oxide synthase
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
PY - 2010/1/1
Y1 - 2010/1/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=77949317723&partnerID=8YFLogxK
U2 - 10.3346/jkms.2010.25.1.16
DO - 10.3346/jkms.2010.25.1.16
M3 - Article
C2 - 20052342
AN - SCOPUS:77949317723
VL - 25
SP - 16
EP - 23
JO - Journal of Korean Medical Science
JF - Journal of Korean Medical Science
SN - 1011-8934
IS - 1
ER -