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

التفاصيل البيبلوغرافية
العنوان:	Connexin37-Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II -Mediated Hypertension.
المؤلفون:	Le Gal, L., Pellegrin, M., Santoro, T., Mazzolai, L., Kurtz, A., Meda, P., Wagner, C., Haefliger, J.A.
المصدر:	Journal of the American Heart Association, vol. 8, no. 8, pp. e010823
سنة النشر:	2019
المجموعة:	Université de Lausanne (UNIL): Serval - Serveur académique lausannois
مصطلحات موضوعية:	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, 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
الوصف:	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.
نوع الوثيقة:	article in journal/newspaper
وصف الملف:	application/pdf
اللغة:	English
تدمد:	2047-9980
العلاقة:	info:eu-repo/semantics/altIdentifier/pmid/30943815; info:eu-repo/semantics/altIdentifier/eissn/2047-9980; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_C1CFAC6BE88D0; https://serval.unil.ch/notice/serval:BIB_C1CFAC6BE88DTest; urn:issn:2047-9980; https://serval.unil.ch/resource/serval:BIB_C1CFAC6BE88D.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_C1CFAC6BE88D0Test
DOI:	10.1161/JAHA.118.010823
الإتاحة:	https://doi.org/10.1161/JAHA.118.010823Test https://serval.unil.ch/notice/serval:BIB_C1CFAC6BE88DTest https://serval.unil.ch/resource/serval:BIB_C1CFAC6BE88D.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_C1CFAC6BE88D0Test
حقوق:	info:eu-repo/semantics/openAccess ; CC BY-NC 4.0 ; https://creativecommons.org/licenses/by-nc/4.0Test/
رقم الانضمام:	edsbas.77C5809B
قاعدة البيانات:	BASE

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الوصف
تدمد:	20479980
DOI:	10.1161/JAHA.118.010823