HMG-CoA Reductase Inhibitor Improves Endothelial Dysfunction in Spontaneous Hypertensive Rats Via Down-regulation of Caveolin-1 and Activation of Endothelial Nitric Oxide Synthase.
10.3346/jkms.2010.25.1.16
- Author:
Jung Won SUH
1
;
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
Author Information
1. Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea. djchoi@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Hydroxymethylglutaryl-CoA Reductase Inhibitors;
Caveolins;
Nitric Oxide;
Nitric Oxide Synthase Type III
- MeSH:
Acetylcholine/metabolism;
Animals;
Aorta/metabolism/physiopathology;
Blood Pressure/drug effects;
Caveolin 1/*metabolism;
Down-Regulation;
Drug Administration Schedule;
Endothelium, Vascular/*drug effects/physiopathology;
Fluorobenzenes/administration & dosage/*pharmacology;
Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*pharmacology;
Hypertension/enzymology/metabolism/*physiopathology;
Male;
Nitric Oxide/blood;
Nitric Oxide Synthase Type III/*metabolism;
Phosphorylation;
Pyrimidines/administration & dosage/*pharmacology;
Rats;
Rats, Inbred SHR;
Sulfonamides/administration & dosage/*pharmacology;
Vasodilation/drug effects
- From:Journal of Korean Medical Science
2010;25(1):16-23
- CountryRepublic of Korea
- Language:English
-
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, 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.
