Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria

Impaired blood flow to peripheral tissues during advanced age is associated with endothelial dysfunction and diminished bioavailability of nitric oxide (NO). However, it is unknown whether aging impacts coupling between intracellular calcium ([Ca 2+ ] i) signaling and small- and intermediate K + channel (SK Ca /IK Ca) activity during endothelium-derived hyperpolarization (EDH), a signaling pathway integral to dilation of the resistance vasculature. To address the potential impact of aging on EDH, Fura-2 photometry and intracellular recording were applied to evaluate [Ca 2+ ] i and membrane potential of intact endothelial tubes (width, 60 μm; length, 1-3 mm) freshly isolated from superior epigastric arteries of young (4-6 mo) and old (24-26 mo) male C57BL/6 mice. In response to acetylcholine, intracellular release of Ca 2+ from the endoplasmic reticulum (ER) was enhanced with aging. Further, treatment with the mitochondrial uncoupler FCCP evoked a significant increase of [Ca 2+ ] i with membrane hyperpolarization in an SK Ca /IK Ca -dependent manner in the endothelium of old but not young mice. We conclude that the ability of resistance artery endothelium to release Ca 2+ from intracellular stores (ie, ER and mitochondria) and hyperpolarize V m via SK Ca /IK Ca activation is augmented as compensation for reduced NO bioavailability during advanced age.