Connexin43-dependent mechanism modulates renin secretion and hypertension
Jacques-Antoine Haefliger, … , Klaus Willecke, Paolo Meda
Jacques-Antoine Haefliger, … , Klaus Willecke, Paolo Meda
Published February 1, 2006
Citation Information: J Clin Invest. 2006;116(2):405-413. https://doi.org/10.1172/JCI23327.
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Research Article Nephrology

Connexin43-dependent mechanism modulates renin secretion and hypertension

Abstract

To investigate the function of Cx43 during hypertension, we studied the mouse line Cx43KI32 (KI32), in which the coding region of Cx32 replaces that of Cx43. Within the kidneys of homozygous KI32 mice, Cx32 was expressed in cortical and medullary tubules, as well as in some extra- and intraglomerular vessels, i.e., at sites where Cx32 and Cx43 are found in WT mice. Under such conditions, renin expression was much reduced compared with that observed in the kidneys of WT and heterozygous KI32 littermates. After exposure to a high-salt diet, all mice retained a normal blood pressure. However, whereas the levels of renin were significantly reduced in the kidneys of WT and heterozygous KI32 mice, reaching levels comparable to those observed in homozygous littermates, they were not further affected in the latter animals. Four weeks after the clipping of a renal artery (the 2-kidney, 1-clip [2K1C] model), 2K1C WT and heterozygous mice showed an increase in blood pressure and in the circulating levels of renin, whereas 2K1C homozygous littermates remained normotensive and showed unchanged plasma renin activity. Hypertensive, but not normotensive, mice also developed cardiac hypertrophy. The data indicate that replacement of Cx43 by Cx32 is associated with decreased expression and secretion of renin, thus preventing the renin-dependent hypertension that is normally induced in the 2K1C model.

Authors

Jacques-Antoine Haefliger, Nathalie Krattinger, David Martin, Thierry Pedrazzini, Alessandro Capponi, Britta Döring, Achim Plum, Anne Charollais, Klaus Willecke, Paolo Meda

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Figure 1

Cx43 and Cx32 were differentially distributed in the kidneys of KI32 mice.

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Cx43 and Cx32 were differentially distributed in the kidneys of KI32 mic...
(A–D) Antibodies (A, C, and D) and a lacZ reporter gene construct (B) revealed the presence of Cx43 between the ECs of both interlobular renal arterioles (D) and afferent arterioles (B and C). Cx43 was also expressed by the ECs of the glomeruli (A and B). (E) In contrast, antibodies against Cx32 showed no staining of glomeruli and arterioles, but abundant levels of Cx32 in cortical proximal tubules. (F) In kidneys of homozygous KI32 mice, Cx32 was immunolocalized in both proximal and distal convoluted tubules, as well as in ECs of glomeruli. (G) The protein was also immunolabeled at gap junctions of ECs in interlobular arteries. In these vessels, the protein A–coated gold particles that were reacted with the Cx32 antibodies selectively decorated minute areas of apposition between EC membranes characteristic of gap junctions. g, glomerulus; aa, afferent arteriole; md, macula densa; ila, interlobular arteriole; pct, proximal convoluted tubule; dct, distal convoluted tubule; ec, endothelial cells. Scale bar: 30 μm (A, C, D, and G); 50 μm (B and E); 20 μm (F); 215 nm (H).