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Defective Cx40 Maintains Cx37 Expression but Intact Cx40 Is Crucial for Conducted Dilations Irrespective of Hypertension
- Source :
- Hypertension. 60:1422-1429
- Publication Year :
- 2012
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2012.
-
Abstract
- The gap junction channel protein connexin40 (Cx40) is crucial in vascular and renal physiology, because Cx40-deficient mice exhibit impaired conduction of endothelium-dependent dilations and pronounced hypertension. The latter precludes mechanistic insights into the role of endothelial Cx40, because long-lasting hypertension itself may affect conduction and Cx expression. We aimed to identify endothelial Cx40 functions, their dependency on the conductive capability, and to separate these from hypertension-related alterations. We assessed conduction and Cx expression in mice with cell type–specific deletion of Cx40 and in mice expressing a defective Cx40 (Cx40A96S) identified in humans, which forms nonconducting gap junction channels. Confined arteriolar stimulation with acetylcholine or bradykinin elicited local dilations that conducted upstream without attenuation of the amplitude for distances up to 1.2-mm in controls with a floxed Cx40 gene (Cx40 fl/fl ). Conducted responses in hypertensive animals devoid of Cx40 in renin-producing cells were unaltered but remote dilations were reduced in normotensive animals deficient for Cx40 in endothelial cells (Cx40 fl/fl :Tie2-Cre). Surprisingly, Cx37 expression was undetectable by immunostaining in arteriolar endothelium only in Cx40 fl/fl :Tie2-Cre; however, transcriptional activity of Cx37 in the cremaster was comparable with Cx40 fl/fl controls. Cx40A96S mice were hypertensive with preserved expression of Cx40 and Cx37. Nevertheless, conducted responses were blunted. We conclude that endothelial Cx40 is necessary to support conducted dilations initiated by endothelial agonists and to locate Cx37 into the plasma membrane. These functions are unaltered by long-lasting hypertension. In the presence of a nonconducting Cx40, Cx37 is present but cannot support the conduction highlighting the importance of endothelial Cx40.
- Subjects :
- medicine.medical_specialty
Endothelium
Bradykinin
Connexin
Blood Pressure
Mice, Transgenic
Stimulation
Biology
Connexins
Microcirculation
Mice
chemistry.chemical_compound
Heart Rate
Internal medicine
Internal Medicine
medicine
Animals
Gap junction
Endothelial Cells
Gap Junctions
Acetylcholine
Vasodilation
medicine.anatomical_structure
Endocrinology
chemistry
Hypertension
Endothelium, Vascular
Immunostaining
medicine.drug
Subjects
Details
- ISSN :
- 15244563 and 0194911X
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Hypertension
- Accession number :
- edsair.doi.dedup.....6fbee2cf51f8d3939c4b4d7e57e7381c