PMID- 19109587
OWN - NLM
STAT- MEDLINE
DCOM- 20090429
LR  - 20231213
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 75
IP  - 5
DP  - 2009 Mar
TI  - Substitution of connexin40 with connexin45 prevents hyperreninemia and attenuates 
      hypertension.
PG  - 482-9
LID - 10.1038/ki.2008.637 [doi]
AB  - Connexins (Cxs) are a family of transmembrane proteins that form gap junctions 
      with unique and redundant biophysical functions. Juxtaglomerular cells express 
      Cx40, which is crucial to the control of renin secretion by blood pressure and 
      angiotensin II, and mice that lack Cx40 have high plasma renin and hypertension. 
      To examine whether normal juxtaglomerular cell function depends on the unique 
      properties of Cx40, we measured renin release in mice where the coding sequence 
      for Cx40 was replaced by that for Cx45, using the knock-in method. We first found 
      that the knock-in strategy indeed resulted in expression of Cx45 but not Cx40 in 
      the juxtaglomerular cells of these mice. The plasma renin concentration of the 
      knock-in mice was similar to that in wild-type mice. The high blood pressure of 
      the Cx40 knockout mice was significantly reduced when Cx45 was knocked into the 
      locus but remained mildly elevated compared to wild-type mice. Blockade of 
      angiotensin II formation by enalapril increased the plasma renin concentration in 
      wild-type and the Cx45 knock-in mice but not in the Cx40 knockout mice. Infusion 
      of angiotensin II into isolated perfused kidneys results in decreased renin 
      release, a phenomenon that was attenuated in the Cx40 knockout mice. However, in 
      the Cx45 knock-in mice, angiotensin II suppressed renin release similar to its 
      effect in wild type mice. Unilateral renal artery stenosis increased the plasma 
      renin concentration and blood pressure in both the wild-type and the Cx45 
      knock-in mice but not in the Cx40 knockout mice. Since Cx40 can be replaced by 
      Cx45, a connexin with a significantly lower conductivity, we suggest that the 
      regulation of renin release is not dependent on the unique electrical properties 
      of these channel proteins.
FAU - Schweda, Frank
AU  - Schweda F
AD  - Institute of Physiology, University of Regensburg, Regensburg, Germany. 
      frank.schweda@klinik.uni-regensburg.de
FAU - Kurtz, Lisa
AU  - Kurtz L
FAU - de Wit, Cor
AU  - de Wit C
FAU - Janssen-Bienhold, Ulrike
AU  - Janssen-Bienhold U
FAU - Kurtz, Armin
AU  - Kurtz A
FAU - Wagner, Charlotte
AU  - Wagner C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081224
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Connexins)
RN  - 0 (connexin 45)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
CIN - Kidney Int. 2009 Mar;75(5):460-2. PMID: 19219002
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Connexins/*deficiency/*genetics
MH  - Gene Knock-In Techniques
MH  - Genetic Therapy
MH  - Hypertension/*therapy
MH  - Juxtaglomerular Apparatus/cytology
MH  - Kidney/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Renin/*blood
MH  - Gap Junction alpha-5 Protein
EDAT- 2008/12/26 09:00
MHDA- 2009/04/30 09:00
CRDT- 2008/12/26 09:00
PHST- 2008/12/26 09:00 [entrez]
PHST- 2008/12/26 09:00 [pubmed]
PHST- 2009/04/30 09:00 [medline]
AID - S0085-2538(15)53737-X [pii]
AID - 10.1038/ki.2008.637 [doi]
PST - ppublish
SO  - Kidney Int. 2009 Mar;75(5):482-9. doi: 10.1038/ki.2008.637. Epub 2008 Dec 24.