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Deficiency of the T‐type Calcium Channel Ca v 3.1 Attenuates Endothelial Dysfunction in Aging Mice
Author(s) -
Hansen Pernille,
Andersen Kenneth,
Vanhoutte Paul,
Thuesen Anne
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.786.3
Subject(s) - myograph , medicine , endocrinology , endothelial dysfunction , vasoconstriction , mesenteric arteries , contraction (grammar) , l type calcium channel , acetylcholine , constriction , voltage dependent calcium channel , endothelium , electrical impedance myography , vasodilation , calcium , calcium channel , chemistry , artery
Background T‐type calcium channels are involved in vasoconstriction. Furthermore, these channels play a larger role in contraction of vascular smooth muscle under increased oxidative stress. It was therefore hypothesized that T‐type channels contribute to the endothelial dysfunction during old age. Method: The endothelial function was tested in young and one year old Wt and Ca v 3.1‐/‐ mice. Mesenteric blood vessels were perfused and changes in luminal diameter were determined. Aortae were isolated, suspended in a wire‐myograph and changes in tension were determined. Results: Depolarization by high K + induced a constriction followed by secondary dilatation (recovery) in mesenteric vessels. The recovery was significantly diminished in Wt mice with age. By contrast, recovery was significantly increased with age in KO mice. Pretreatment with L‐NAME abolished recovery. The initial constriction was not different between Wt and KO mice. Aortae were precontracted by high K + (EC70) with no difference between young and old mice. Acetylcholine‐induced relaxations in aortae were significantly smaller (abolished) in old compared to young Wt mice. By contrast, there was no difference in the aortic response to acetylcholine between old and young KO mice. Conclusion T‐type calcium channel deficient mice are protected against age‐dependent endothelial dysfunction as arteries of T‐type deficient mice do not develop decreased recovery and reduced responses to acetylcholine with age. This is in line with studies suggesting that T‐type blockers have a protective effect against endothelial dysfunction in hypertensive patients. Foundation: Danish Research Council and Danish Heart Foundation.