PMID- 25712722
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20231213
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 65
IP  - 4
DP  - 2015 Apr
TI  - Interplay between connexin40 and nitric oxide signaling during hypertension.
PG  - 910-5
LID - 10.1161/HYPERTENSIONAHA.114.04775 [doi]
AB  - Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the 
      adaptation of endothelial and smooth muscle cells to hemodynamic changes. To 
      decipher the in vivo interplay between these proteins, we studied Cx40-null mice, 
      a model of renin-dependent hypertension which displays an altered 
      endothelium-dependent relaxation of the aorta because of reduced eNOS levels. 
      These mice, which were either untreated or subjected to the 1-kidney, 1-clip 
      (1K1C) procedure, a model of volume-dependent hypertension, were compared with 
      control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) 
      procedure, a model of renin-dependent hypertension. All operated mice became 
      hypertensive and featured hypertrophy and altered Cx expression of the aorta. The 
      combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice 
      raised blood pressure and cardiac weight index. Under these conditions, all 
      aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and 
      Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between 
      Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The 
      Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also 
      featured decreased levels of eNOS. In these animals, the volume overload caused 
      by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a 
      higher NO release. The findings provide evidence that Cx40 and Cx37 play an in 
      vivo role in the regulation of eNOS.
CI  - (c) 2015 American Heart Association, Inc.
FAU - Le Gal, Loic
AU  - Le Gal L
AD  - From the Departments of Medicine (L.L.G., F.A., J.-A.H.) and Angiology (L.M.), 
      Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 
      Switzerland; and Department of Cell Physiology and Metabolism, University of 
      Geneva, Medical Center, Geneva, Switzerland (P.M.).
FAU - Alonso, Florian
AU  - Alonso F
AD  - From the Departments of Medicine (L.L.G., F.A., J.-A.H.) and Angiology (L.M.), 
      Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 
      Switzerland; and Department of Cell Physiology and Metabolism, University of 
      Geneva, Medical Center, Geneva, Switzerland (P.M.).
FAU - Mazzolai, Lucia
AU  - Mazzolai L
AD  - From the Departments of Medicine (L.L.G., F.A., J.-A.H.) and Angiology (L.M.), 
      Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 
      Switzerland; and Department of Cell Physiology and Metabolism, University of 
      Geneva, Medical Center, Geneva, Switzerland (P.M.).
FAU - Meda, Paolo
AU  - Meda P
AD  - From the Departments of Medicine (L.L.G., F.A., J.-A.H.) and Angiology (L.M.), 
      Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 
      Switzerland; and Department of Cell Physiology and Metabolism, University of 
      Geneva, Medical Center, Geneva, Switzerland (P.M.).
FAU - Haefliger, Jacques-Antoine
AU  - Haefliger JA
AD  - From the Departments of Medicine (L.L.G., F.A., J.-A.H.) and Angiology (L.M.), 
      Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 
      Switzerland; and Department of Cell Physiology and Metabolism, University of 
      Geneva, Medical Center, Geneva, Switzerland (P.M.). 
      Jacques-Antoine.Haefliger@chuv.ch.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150223
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Connexins)
RN  - 63231-63-0 (RNA)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Animals
MH  - Blood Pressure/*physiology
MH  - Connexins/biosynthesis/*genetics
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/*metabolism/physiopathology
MH  - *Gene Expression Regulation
MH  - Hypertension/*genetics/metabolism/physiopathology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type III/biosynthesis/*genetics
MH  - RNA/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Gap Junction alpha-5 Protein
OTO - NOTNLM
OT  - 1-kidney, 1-clip (1K1C)
OT  - connexins
OT  - endothelial cells
OT  - endothelial nitric oxide synthase
OT  - gap junctions
OT  - hypertension
EDAT- 2015/02/26 06:00
MHDA- 2015/05/13 06:00
CRDT- 2015/02/26 06:00
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - HYPERTENSIONAHA.114.04775 [pii]
AID - 10.1161/HYPERTENSIONAHA.114.04775 [doi]
PST - ppublish
SO  - Hypertension. 2015 Apr;65(4):910-5. doi: 10.1161/HYPERTENSIONAHA.114.04775. Epub 
      2015 Feb 23.