Aging is associated with vascular dysfunction that impairs tissue perfusion, physical activity and the quality of life. Calcium signaling in endothelial cells (ECs) is integral to vasomotor control, exemplified by localized Ca2+ signals within EC projections through holes in the internal elastic lamina (IEL). Within these microdomains, endothelial-derived hyperpolarization is integral to smooth muscle cell (SMC) relaxation via coupling through myoendothelial gap junctions. However the effects of aging on local EC Ca2+ signals (and thereby signaling between ECs and SMCs) remain unclear, nor have these events been investigated in vivo. Further, it is unknown whether aging affects either the number or size of IEL holes. In the present study, we tested the hypothesis that local EC Ca2+ signaling is impaired with advanced age along with a reduction in IEL holes. In anesthetized mice expressing a Ca2+-sensitive fluorescent protein (GCaMP2) selectively in ECs, our findings illustrate that for mesenteric arteries (MAs) controlling splanchnic blood flow, the frequency of spontaneous local Ca2+ signals in ECs was reduced by ~85% in old (24-26 months) vs. young (3-6 months) animals. At the same time, the number (and total area) of holes per mm-2 of IEL was reduced by ~40%. We suggest that diminished signaling between ECs and SMCs contributes to dysfunction of resistance arteries with advanced age.
- internal elastic lamina
- myoendothelial signaling
- Copyright © 2016, American Journal of Physiology - Heart and Circulatory Physiology