TY - JOUR
T1 - Age-dependent impact of CaV3.2 T-type calcium channel deletion on myogenic tone and flow-mediated vasodilatation in small arteries
AU - Mikkelsen, Miriam F.
AU - Björling, Karl
AU - Jensen, Lars Jørn
N1 - This article is protected by copyright. All rights reserved.
PY - 2016
Y1 - 2016
N2 - The myogenic response and flow-mediated vasodilatation are important regulators of local blood perfusion and total peripheral resistance, and are known to entail a calcium influx into vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), respectively. CaV3.2 T-type calcium channels are expressed in both VSMCs and ECs of small arteries. The T-type channels are important drug targets but due to the lack of specific antagonists our understanding of the role of CaV3.2 channels in vasomotor tone at various ages is scarce. We evaluated the myogenic response, flow-mediated vasodilatation, structural remodeling, and mRNA + protein expression in small mesenteric arteries from CaV3.2 knock-out vs. wild-type mice at young vs. mature adult age. In young mice, only, deletion of CaV3.2 led to enhanced myogenic response and ∼50 % reduction of flow-mediated vasodilatation. Ni(2+) had both CaV3.2-dependent and -independent effects. No changes in mRNA expression of several important K(+) and Ca(2+) channel genes were induced by CaV3.2 knock-out. However, the expression of the other T-type channel isoform (CaV3.1) was reduced at the mRNA and protein level in mature adult compared to young WT arteries. Our study shows important roles of the CaV3.2 T-type calcium channels in myogenic tone and flow-mediated vasodilation that disappear with aging. Since increased arterial tone is a risk factor for cardiovascular disease we conclude that CaV3.2 channels, by modulating pressure- and flow-mediated vasomotor responses to prevent excess arterial tone, protect against cardiovascular disease.
AB - The myogenic response and flow-mediated vasodilatation are important regulators of local blood perfusion and total peripheral resistance, and are known to entail a calcium influx into vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), respectively. CaV3.2 T-type calcium channels are expressed in both VSMCs and ECs of small arteries. The T-type channels are important drug targets but due to the lack of specific antagonists our understanding of the role of CaV3.2 channels in vasomotor tone at various ages is scarce. We evaluated the myogenic response, flow-mediated vasodilatation, structural remodeling, and mRNA + protein expression in small mesenteric arteries from CaV3.2 knock-out vs. wild-type mice at young vs. mature adult age. In young mice, only, deletion of CaV3.2 led to enhanced myogenic response and ∼50 % reduction of flow-mediated vasodilatation. Ni(2+) had both CaV3.2-dependent and -independent effects. No changes in mRNA expression of several important K(+) and Ca(2+) channel genes were induced by CaV3.2 knock-out. However, the expression of the other T-type channel isoform (CaV3.1) was reduced at the mRNA and protein level in mature adult compared to young WT arteries. Our study shows important roles of the CaV3.2 T-type calcium channels in myogenic tone and flow-mediated vasodilation that disappear with aging. Since increased arterial tone is a risk factor for cardiovascular disease we conclude that CaV3.2 channels, by modulating pressure- and flow-mediated vasomotor responses to prevent excess arterial tone, protect against cardiovascular disease.
U2 - 10.1113/JP271470
DO - 10.1113/JP271470
M3 - Journal article
C2 - 26752249
VL - 594
SP - 5881
EP - 5898
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 20
ER -