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 5

Heart weight increased in control and heterozygous KI32 mice, but not in homozygous littermates.

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Heart weight increased in control and heterozygous KI32 mice, but not in...
(A) Immunofluorescence labeling for Cx43 and Cx32 showed the exclusive presence of the former and latter connexins in sections of ventricular myocytes of WT and homozygous KI32 mice, respectively. In the myocardium of heterozygous littermates, the 2 connexins colocalized at intercalated discs. Bar: 120 μm. (B) Four weeks after clipping of a renal artery, the cardiac weight index of WT, 2K1C mice that were hypertensive (white bar) was higher than that of sham-operated controls that remained normotensive (black bar), reflecting cardiac hypertrophy. Similar observations were made in heterozygous 2K1C mice. In contrast, no change in cardiac index was observed in homozygous 2K1C littermates. Data are mean ± SEM values of the number of mice indicated in Table 1. White bars, 2K1C mice; black bars, sham-operated mice. *P < 0.05; ***P < 0.001.