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Variable Contribution of TMEM 16A to Tone in Murine Arterial Vasculature
Author(s) -
Jensen Anders Bisgaard,
Joergensen Henrik Black,
Dam Vibeke Secher,
Kamaev Dmitrii,
Boedtkjer Donna,
Füchtbauer ErnstMartin,
Aalkjaer Christian,
Matchkov Vladimir V.
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12984
Subject(s) - mesenteric arteries , aorta , vascular smooth muscle , endocrinology , medicine , blood pressure , blood vessel , chemistry , coronary arteries , artery , anatomy , smooth muscle
TMEM 16A is essential for Ca 2+ ‐activated Cl − conductance in vascular smooth muscle. The importance of TMEM 16A for agonist‐induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that TMEM 16A might have a complex cellular function beyond being essential for the Ca 2+ ‐activated Cl − conductance, for example modulation of Ca 2+ channel expression. Mice with constitutive, smooth muscle‐specific expression of si RNA directed against Tmem16a (transgenic mice, TG ) were generated. Isometric constrictions of isolated aorta, mesenteric, femoral and tail arteries from TG mice were compared with wild‐types. Protein expression was analysed by Western blots. Blood pressure and heart rate were studied telemetrically. Significant TMEM 16A down‐regulation was seen in aorta and tail arteries, while no changes were detected in mesenteric and femoral arteries. Contractile responses of mesenteric and femoral arteries from TG and wild‐type mice were not different. Aorta from TG mice showed reduced agonist‐induced constriction, while their responses to elevated K + were unchanged. Tail arteries from TG mice also constricted less to adrenergic stimulation than wild‐types. Surprisingly, tail arteries from TG mice constricted less to elevated K + too and were more sensitive to nifedipine‐induced relaxation. Consistently, TMEM 16A down‐regulation in tail arteries was associated with reduction in CACNA 1C protein (i.e. vascular L‐type Ca 2+ channel) expression. No differences in blood pressure and heart rate between the groups were seen. This study suggests a complex contribution of TMEM 16A in vascular function. We suggest that TMEM 16A modulates arterial contractility, at least in part, indirectly via regulation of CACNA 1C expression.