Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function.

Area of Science:

• Cardiovascular Physiology
• Aging Research
• Endothelial Function

Background:

• Age-related endothelial dysfunction is a significant health concern.
• Oxidative stress and phenotypic alterations are implicated in this dysfunction.
• Coronary arterioles are critical for regulating myocardial blood flow.

Purpose of the Study:

• To investigate the role of oxidative stress and phenotypic changes in age-related endothelial dysfunction of rat coronary arterioles.
• To identify specific molecular mechanisms contributing to impaired vasodilation in aged vessels.

Main Methods:

• Isolation and videomicroscopic assessment of coronary arterioles from young and aged rats.
• Measurement of superoxide anion (O(2)(.-)) generation using lucigenin chemiluminescence.
• Analysis of protein and mRNA expression of key enzymes (e.g., NOS, COX, SOD) via Western blotting and RT-PCR.
• Assessment of in vivo peroxynitrite formation using immunohistochemistry.

Main Results:

• Aged arterioles exhibited significantly impaired flow-induced dilation, which was nitric oxide synthase-dependent and ameliorated by antioxidants.
• Increased O(2)(.-) generation was observed in aged vessels, originating from both endothelial and smooth muscle cells.
• Aged arterioles showed decreased expression of endothelial nitric oxide synthase (eNOS) and increased expression of inducible nitric oxide synthase (iNOS).
• Evidence of increased in vivo peroxynitrite formation was found in aged arterioles.

Conclusions:

• Aging induces phenotypic changes in coronary arterioles, characterized by increased oxidative stress and altered nitric oxide signaling.
• These changes, including increased iNOS and reduced eNOS, contribute to impaired nitric oxide-mediated vasodilation and endothelial dysfunction.
• Oxidative stress, particularly superoxide production, plays a key role in the age-related decline of vascular function.