| Autor: |
Polk, Felipe D., Hakim, Md A., Silva, Josiane F., Behringer, Erik J., Pires, Paulo W. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Dec2023, Vol. 325 Issue 6, pH1360-H1372, 13p |
| Abstrakt: |
Aging is associated with cognitive decline via incompletely understood mechanisms. Cerebral microvascular dysfunction occurs in aging, particularly impaired endothelium-mediated dilation. Parenchymal arterioles are bottlenecks of cerebral microcirculation, and dysfunction causes a mismatch in nutrient demand and delivery, leaving neurons at risk. Extracellular nucleotides elicit parenchymal arteriole dilation by activating endothelial purinergic receptors (P2Y), leading to the opening of K+ channels, including inwardly rectifying K+ channels (Kir2). These channels amplify hyperpolarizing signals, resulting in dilation. However, it remains unknown if endothelial P2Y and Kir2 signaling are altered in brain parenchymal arterioles during aging. We hypothesized that aging impairs endothelial P2Y and Kir2 function in parenchymal arterioles. We observed reduced dilation to the purinergic agonist 2-methyl-S-ADP (1 μM) in arterioles from aged (>24 mo old) mice when compared with young (4-6 mo of age) despite similar hyperpolarization in endothelial cell tubes. No differences were observed in vasodilation or endothelial cell hyperpolarization to activation of small- and intermediate-conductance Ca2+-activated K+ channels (KCa2.3/KCa3.1) by NS309. Hyperpolarization to 15 mM [K+]e was smaller in aged than young mice, despite a paradoxically increased dilation in aged arterioles to 15 mM [K+]e that was unchanged by endothelium removal. Kir2 inhibition attenuated vasodilatory responses to 15 mM [K+]e and 1 #956;M 2-me-S-ADP in both young and aged arterioles. Furthermore, we observed a significant increase in myogenic tone in aged parenchymal arterioles, which was not enhanced by endothelium removal. We conclude that aging impairs endothelial Kir2 channel function in the cerebral microcirculation with possible compensation by smooth muscle cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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