Erika M Boerman1, Steven S Segal1,2. 1. Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA. 2. Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
Abstract
OBJECTIVE: Aging impairs MA dilation by reducing the ability of sensory nerves to counteract sympathetic vasoconstriction. This study tested whether altered SMC Ca2+ 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 Ca2+ 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 Ca2+ spark sites with no difference in Ca2+ 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 Ca2+ 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 Ca2+ signaling underlying vasomotor control during sympathetic activation.
OBJECTIVE: Aging impairs MA dilation by reducing the ability of sensory nerves to counteract sympathetic vasoconstriction. This study tested whether altered SMC Ca2+ 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 Ca2+ 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 Ca2+ spark sites with no difference in Ca2+ 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 Ca2+ 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 Ca2+ signaling underlying vasomotor control during sympathetic activation.
Authors: Matthew J Socha; Erika M Boerman; Erik J Behringer; Rebecca L Shaw; Timothy L Domeier; Steven S Segal Journal: J Physiol Date: 2015-03-19 Impact factor: 5.182
Authors: M Löhn; W Jessner; M Fürstenau; M Wellner; V Sorrentino; H Haller; F C Luft; M Gollasch Journal: Circ Res Date: 2001-11-23 Impact factor: 17.367