Aging alters spontaneous and neurotransmitter-mediated Ca(2+) signaling in smooth muscle cells of mouse mesenteric arteries.

OBJECTIVE: Aging impairs MA dilation by reducing the ability of sensory nerves to counteract sympathetic vasoconstriction. This study tested whether altered SMC Ca(2+) signals to sympathetic (NE) and sensory (CGRP) neurotransmitters underlie aging-related deficits in vasodilation. METHODS: MAs from young and old mice were pressurized and loaded with Fluo-4 dye for confocal measurement of SMC Ca(2+) sparks and waves. Endothelial denudation resolved the influence of ECs. SMCs were immunolabeled for RyR isoforms and compared with transcript levels for RyRs and CGRP receptor components. RESULTS: SMCs from young vs old mice exhibited more spontaneous Ca(2+) spark sites with no difference in Ca(2+) waves. NE reduced spark sites and increased waves for both groups; addition of CGRP restored sparks and reduced waves only for young mice. Endothelial denudation attenuated Ca(2+) responses to CGRP for young but not old mice, which were already attenuated, suggesting a diminished role for ECs with aging. CGRP receptor expression was similar between ages with increased serum CGRP in old mice, where RyR1 expression was replaced by RyR3. CONCLUSION: With aging, we suggest that altered RyR expression in SMCs contributes to impaired ability of sensory neurotransmission to restore Ca(2+) signaling underlying vasomotor control during sympathetic activation.