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The connexin 40 A96S mutation causes renin-dependent hypertension
Indra Lübkemeier1, Katharina Machura, Lisa Kurtz
1Institute of Genetics, University of Bonn, Bonn, Germany.
Journal of the American Society of Nephrology : JASN
|May 21, 2011
Summary
The A96S connexin40 (CX40) mutation causes renin-dependent hypertension in mice. This CX40 variant impairs pressure-mediated inhibition of renin secretion, leading to elevated blood pressure.
Area of Science:
- Cardiovascular Physiology
- Renal Physiology
- Molecular Biology
Background:
- Connexin40 (CX40) is a gap-junction protein crucial for cardiovascular function.
- CX40 deletion causes hypertension; human variants like A96S require investigation for hypertensive potential.
Purpose of the Study:
- To investigate if the human A96S variant in connexin40 (CX40) promotes hypertension in mice.
- To elucidate the role of CX40 in regulating renin secretion and blood pressure.
Main Methods:
- Generated mice with the A96S variant in the mouse connexin40 gene.
- Assessed blood pressure, plasma renin concentration, and renin mRNA levels.
- Examined renin-expressing cell localization and renin secretion from isolated kidneys.
Main Results:
- Homozygous A96S mice exhibited hypertension, significantly elevated plasma renin concentrations, and increased renin mRNA levels.
- Renin-expressing cells showed aberrant localization outside the afferent arteriole media.
- Isolated kidneys from A96S mice failed to inhibit renin secretion in response to increased perfusion pressure.
Conclusions:
- The A96S mutation in connexin40 (CX40) induces renin-dependent hypertension in mice.
- Functional CX40 is essential for blood pressure modulation of renin secretion.
- Aberrant renin cell localization in A96S mice impairs pressure-mediated renin inhibition.
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