Le Gal, Loic and Pellegrin, Maxime and Santoro, Tania and Mazzolai, Lucia and Kurtz, Armin and Meda, Paolo and Wagner, Charlotte and Haefliger, Jacques-Antoine (2019) Connexin37-Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II-Mediated Hypertension. JOURNAL OF THE AMERICAN HEART ASSOCIATION, 8 (8): e010823. ISSN 2047-9980,
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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 (AT2R), and increased transcripts levels of downstream signaling proteins, such as Cnksrl and Ptpn6 (SHP-1). Accordingly, the response of Cx37-/- mice aortas to an ex vivo Angll exposure was altered, since phosphorylation levels of several proteins of the Angll pathway (MLC2, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMOOTH-MUSCLE; BLOOD-PRESSURE; TYPE-2 RECEPTORS; CONNEXIN 40; CX40; OVEREXPRESSION; VASODILATION; HYPERPLASIA; EXPRESSION; PROTEINS; angiotensin II; aorta; connexins; endothelial cells; hypertension; kidney; smooth muscle cells |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2020 05:56 |
| Last Modified: | 14 Apr 2020 05:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27158 |
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