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Published on: August 13, 2019
Raloxifene protects endothelial cell function against oxidative stress.
C M Wong1, L M Yung, F P Leung
1Institute of Vascular Medicine and Department of Physiology, Chinese University of Hong Kong, Hong Kong, China.
British Journal of Pharmacology
|June 25, 2008
Summary
Raloxifene protects against oxidative stress-induced endothelial dysfunction by enhancing nitric oxide (NO) bioavailability. This selective oestrogen receptor modulator increases Akt and endothelial nitric oxide synthase (eNOS) phosphorylation, improving vascular tone.
Area of Science:
- Cardiovascular Physiology
- Endothelial Biology
- Pharmacology
Background:
- Vascular tone regulation depends on balancing nitric oxide (NO) and reactive oxygen species (ROS).
- Increased ROS impairs endothelial function by reducing NO bioavailability.
- Oxidative stress is implicated in endothelial dysfunction.
Purpose of the Study:
- To investigate if raloxifene, a selective oestrogen receptor modulator, can prevent endothelial dysfunction induced by oxidative stress.
- To elucidate the mechanism by which raloxifene exerts its protective effects.
Main Methods:
- Isometric tension measurements in rat aortic rings.
- Assessment of cyclic guanosine monophosphate (cGMP) levels via radioimmunoassay.
- Western blot analysis for phosphorylated endothelial nitric oxide synthase (p-eNOS) and Akt.
Main Results:
- Raloxifene ameliorated impaired relaxations in aortic rings exposed to ROS.
- Raloxifene restored ACh-stimulated cGMP levels suppressed by ROS.
- Raloxifene increased Akt and eNOS phosphorylation, an effect blocked by ICI 182,780 and PI3K inhibitors.
Conclusions:
- Raloxifene effectively counteracts oxidative stress-induced endothelial dysfunction in vitro.
- The protective mechanism involves an ICI 182,780-sensitive pathway activating Akt and eNOS.
- Raloxifene enhances endothelial function through increased NO signaling, not direct ROS scavenging.
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