Endothelial K_IR2 channel dysfunction in aged cerebral parenchymal arterioles

Area of Science:

• Neuroscience
• Cardiovascular Science
• Aging Research

Background:

• Aging is linked to cognitive decline through poorly understood mechanisms.
• Cerebral microvascular dysfunction, especially impaired endothelium-mediated dilation, is a hallmark of aging.
• Parenchymal arteriole dysfunction disrupts nutrient supply to neurons, increasing their vulnerability.

Purpose of the Study:

• To investigate if endothelial purinergic receptor (P2Y) and inwardly-rectifying K+ channel (KIR2) signaling are altered in aged brain parenchymal arterioles.
• To test the hypothesis that aging impairs endothelial P2Y and KIR2 function in these vessels.

Main Methods:

• Compared vasodilation and endothelial hyperpolarization in parenchymal arterioles from young and aged mice.
• Utilized purinergic agonists (2-methyl-S-ADP) and K+ channel activators (NS309, high K+).
• Assessed the role of KIR2 channels using specific inhibitors and evaluated myogenic tone.

Main Results:

• Aged arterioles showed reduced dilation to 2-methyl-S-ADP, indicating impaired P2Y/KIR2 signaling.
• No differences in dilation or hyperpolarization were observed with KCa channel activation.
• Aged arterioles exhibited increased myogenic tone and impaired hyperpolarization to high K+, despite paradoxical vasodilation.

Conclusions:

• Aging impairs endothelial KIR2 channel function in cerebral parenchymal arterioles.
• This dysfunction may contribute to age-related cognitive decline.
• Smooth muscle cells might compensate for impaired endothelial function in aged brains.