Connexin37‐Dependent Mechanisms Selectively Contribute to Modulate Angiotensin II‐Mediated Hypertension

Autor: Armin Kurtz, Loïc Le Gal, Charlotte Wagner, Jacques-Antoine Haefliger, Maxime Pellegrin, Lucia Mazzolai, Paolo Meda, Tania Santoro
Jazyk: angličtina
Rok vydání: 2019
Předmět:
MAPK/ERK pathway
Male
medicine.medical_specialty
kidney
Myosin Light Chains
Myocytes
Smooth Muscle
Blood Pressure
030204 cardiovascular system & hematology
angiotensin II
Receptor
Angiotensin
Type 2
Connexins
Muscle
Smooth
Vascular
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
Renin–angiotensin system
Renin
medicine
Animals
Vasoconstrictor Agents
Enzyme Inhibitors
Receptor
Extracellular Signal-Regulated MAP Kinases
Protein kinase B
Aorta
030304 developmental biology
Original Research
Mice
Knockout
0303 health sciences
Kidney
business.industry
Protein Tyrosine Phosphatase
Non-Receptor Type 6
Endothelial Cells
Angiotensin II
smooth muscle cells
Disease Models
Animal
Angiotensin II/pharmacology
Aorta/cytology
Aorta/drug effects
Aorta/metabolism
Blood Pressure/drug effects
Blood Pressure/genetics
Connexins/genetics
Endothelial Cells/metabolism
Enzyme Inhibitors/pharmacology
Extracellular Signal-Regulated MAP Kinases/metabolism
Hypertension/genetics
Hypertension/metabolism
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
aorta
connexins
endothelial cells
hypertension
Endocrinology
medicine.anatomical_structure
Blood pressure
NG-Nitroarginine Methyl Ester
High Blood Pressure
Hypertension
Phosphorylation
Cardiology and Cardiovascular Medicine
business
Proto-Oncogene Proteins c-akt
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Journal of the American Heart Association, vol. 8, no. 8, pp. e010823
ISSN: 2047-9980
Popis: 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.
Databáze: OpenAIRE
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