Connexin37-Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II -Mediated Hypertension.

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License: CC BY-NC 4.0
Serval ID
serval:BIB_C1CFAC6BE88D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Connexin37-Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II -Mediated Hypertension.
Journal
Journal of the American Heart Association
Author(s)
Le Gal L., Pellegrin M., Santoro T., Mazzolai L., Kurtz A., Meda P., Wagner C., Haefliger J.A.
ISSN
2047-9980 (Electronic)
ISSN-L
2047-9980
Publication state
Published
Issued date
16/04/2019
Peer-reviewed
Oui
Volume
8
Number
8
Pages
e010823
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Background Gap junction channels made of Connexin37 (Cx37) are expressed by aortic endothelial and smooth muscle cells of hypertensive mice, as well as by the renin-secreting cells of kidneys. Methods and Results To decipher whether Cx37 has any role in hypertension, angiotensin II (Ang II ) was infused in normotensive wild-type and Cx37-deficient mice (Cx37-/-). After 2 to 4 weeks, the resulting increase in blood pressure was lower in Cx37-/- than in wild-type mice, suggesting an alteration in the Ang II response. To investigate this possibility, mice were submitted to a 2-kidney, 1-clip procedure, a renin-dependent model of hypertension. Two weeks after this clipping, Cx37-/- mice were less hypertensive than wild-type mice and, 2 weeks later, their blood pressure had returned to control values, in spite of abnormally high plasma renin levels. In contrast, Cx37-/- and wild-type mice that received N-nitro-l-arginine-methyl-ester, a renin-independent model of hypertension, featured a similar and sustained increase in blood pressure. The data indicate that loss of Cx37 selectively altered the Ang II -dependent pathways. Consistent with this conclusion, aortas of Cx37-/- mice featured an increased basal expression of the Ang II type 2 receptors ( AT 2R), and increased transcripts levels of downstream signaling proteins, such as Cnksr1 and Ptpn6 ( SHP -1). Accordingly, the response of Cx37-/- mice aortas to an ex vivo Ang II exposure was altered, since phosphorylation levels of several proteins of the Ang II pathway ( MLC 2, ERK , and AKT ) remained unchanged. Conclusions These findings provide evidence that Cx37 selectively influences Ang II signaling, mostly via a modulation of the expression of the Ang II type 2 receptor.
Keywords
Angiotensin II/pharmacology, Animals, Aorta/cytology, Aorta/drug effects, Aorta/metabolism, Blood Pressure/drug effects, Blood Pressure/genetics, Connexins/genetics, Disease Models, Animal, Endothelial Cells/metabolism, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/metabolism, Hypertension/genetics, Hypertension/metabolism, Male, Mice, Mice, Knockout, Muscle, Smooth, Vascular/cytology, Myocytes, Smooth Muscle/metabolism, Myosin Light Chains/metabolism, NG-Nitroarginine Methyl Ester/pharmacology, Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics, Proto-Oncogene Proteins c-akt/metabolism, Receptor, Angiotensin, Type 2/metabolism, Renin/metabolism, Vasoconstrictor Agents/pharmacology, angiotensin II, aorta, connexins, endothelial cells, hypertension, kidney, smooth muscle cells
Pubmed
Web of science
Open Access
Yes
Create date
22/04/2019 14:35
Last modification date
12/08/2020 5:22
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