Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P01185 (
vasopressin
)
23,126
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A Ca
2+
-activated Cl
-
channel protein,
ANO1
, is expressed in vascular smooth muscle cells where Cl
-
current is thought to potentiate contraction by contributing to membrane depolarization. However, there is an inconsistency between previous knockout and knockdown studies on
ANO1
's role in small arteries. In this study, we assessed cardiovascular function of heterozygous mice with global deletion of exon 7 in the
ANO1
gene. We found decreased expression of
ANO1
in aorta, saphenous and tail arteries from heterozygous
ANO1
knockout mice in comparison with wild type. Accordingly,
ANO1
knockdown reduced the Ca
2+
-activated Cl
-
current in smooth muscle cells. Consistent with conventional hypothesis, the contractility of aorta from
ANO1
heterozygous mice was reduced. Surprisingly, we found an enhanced contractility of tail and saphenous arteries from
ANO1
heterozygous mice when stimulated with noradrenaline,
vasopressin
, and K
+
-induced depolarization. This difference was endothelium-independent. The increased contractility of
ANO1
downregulated small arteries was due to increased Ca
2+
influx. The expression of L-type Ca
2+
channels was not affected but expression of the plasma membrane Ca
2+
ATPase 1 and the Piezo1 channel was increased. Expressional analysis of tail arteries further suggested changes of
ANO1
knockdown smooth muscle cells toward a pro-contractile phenotype. We did not find any difference between genotypes in blood pressure, heart rate, pressor response, and vasorelaxation in vivo. Our findings in tail and saphenous arteries contrast with the conventional hypothesis and suggest additional roles for
ANO1
as a multifunctional protein in the vascular wall that regulates Ca
2+
homeostasis and smooth muscle cell phenotype.
...
PMID:A paradoxical increase of force development in saphenous and tail arteries from heterozygous ANO1 knockout mice. 3324 43
