Aging Alters Spontaneous and Neurotransmitter-mediated Ca Signaling in Smooth Muscle Cells of Mouse Mesenteric Arteries

Overview

Journal Microcirculation

Specialties Biology
Cardiology & Vascular Diseases

Date 2020 Jan 30

PMID 31994289

Citations 3

Authors

Erika M Boerman

Steven S Segal

Affiliations

Soon will be listed here.

Abstract

Objective: Aging impairs MA dilation by reducing the ability of sensory nerves to counteract sympathetic vasoconstriction. This study tested whether altered SMC Ca 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 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 spark sites with no difference in Ca 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 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 signaling underlying vasomotor control during sympathetic activation.

Citing Articles

Impact of aging on vascular ion channels: perspectives and knowledge gaps across major organ systems.

Behringer E Am J Physiol Heart Circ Physiol. 2023; 325(5):H1012-H1038.

PMID: 37624095 PMC: 10908410. DOI: 10.1152/ajpheart.00288.2023.

Functional Role of STIM-1 and Orai1 in Human Microvascular Aging.

El Assar M, Garcia-Rojo E, Sevilleja-Ortiz A, Sanchez-Ferrer A, Fernandez A, Garcia-Gomez B Cells. 2022; 11(22).

PMID: 36429103 PMC: 9688234. DOI: 10.3390/cells11223675.

Differential hyperpolarization to substance P and calcitonin gene-related peptide in smooth muscle versus endothelium of mouse mesenteric artery.

Norton C, Boerman E, Segal S Microcirculation. 2021; 28(8):e12733.

PMID: 34633728 PMC: 9996665. DOI: 10.1111/micc.12733.

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