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Connexin 40 is dispensable for vascular renin cell recruitment but is indispensable for vascular baroreceptor control of renin secretion

  • Organ physiology
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Abstract

Defects of the gap junction protein connexin 40 (Cx40) in renin-secreting cells (RSCs) of the kidney lead to a shift of the localization of RSCs from the media layer of afferent arterioles to the periglomerular interstitium. The dislocation of RSCs goes in parallel with elevated plasma renin levels, impaired pressure control of renin secretion, and hypertension. The reasons for the extravascular shift of RSCs and the blunted pressure regulation of renin secretion caused by the absence of Cx40 are still unclear. We have therefore addressed the question if Cx40 is essential for the metaplastic transformation of preglomerular vascular smooth muscle cells (SMCs) into RSCs and if Cx40 is essential for the pressure control of renin secretion from RSCs located in the media layer of afferent arterioles. For our study, we used mice lacking the angiotensin II type 1A (AT1A) receptors, which display a prominent and reversible salt-sensitive metaplastic transformation of SMCs into RSCs. This mouse line was crossed with Cx40-deficient mice to obtain AT1A and Cx40 double deleted mice. The kidneys of AT1A −/−Cx40−/− mice kept on normal salt (0.3 %) displayed RSCs both in the inner media layer of preglomerular vessels and in the periglomerular interstitium. In contrast to hypotensive AT1A −/− (mean bp syst 112 mmHg) and hypertensive Cx40−/− (mean bp syst 160 mmHg) mice AT1A −/−Cx40−/− mice were normotensive(mean bp syst 130 mmHg). Pressure regulation of renin secretion from isolated kidneys was normal in AT1A −/− mice, but was absent in AT1A −/−Cx40−/− mice alike in Cx40−/− mice. Low-salt diet (0.02 %) increased RSC numbers in the media layer, whilst high-salt diet (4 %) caused disappearance of RSCs in the media layer but not in the periglomerular interstitium. Blood pressure was clearly salt sensitive both in AT1A −/− and in AT1A −/−Cx40−/− mice but was shifted to higher pressure values in the latter genotype. Our data indicate that Cx40 is not a requirement for intramural vascular localization of RSCs nor for reversible metaplastic transformation of SMCs into RSCs. Therefore, the ectopic localization of RSCs in Cx40−/− kidneys is more likely due to a disturbed intercellular communication rather than being the result of chronic overactivation of the renin-angiotensin-aldosterone system or hypertension. Moreover, our findings suggest that Cx40 is a requirement for the pressure control of renin secretion irrespective of the localization of RSCs.

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Acknowledgments

This work was financially supported by the German Research Foundation/Collaborative Research Center SFB 699 and by the German Research Foundation/Grant WA-2137/2-2. The excellent technical assistance provided by Gerda Treuner, Marcela Loza Hilares, Robert Götz, and Anna M’Bangui is gratefully acknowledged. We also thank K. Willecke (Institute for Genetics, University of Bonn, Germany) for providing the Cx40-deficient mouse and T.M. Coffman (Duke University, Durham, North Carolina, USA) for the AT1A-deficient mouse.

Conflict of interest

The authors declared no competing interest.

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Authors and Affiliations

  1. Institut für Physiologie, Universität Regensburg, 93053, Regensburg, Germany

    Katharina Machura, Bjoern Neubauer, Hanna Müller, Philipp Tauber & Armin Kurtz

  2. Department of Internal Medicine, University of Regensburg, Regensburg, Germany

    Lisa Kurtz

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  1. Katharina Machura
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  2. Bjoern Neubauer
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Correspondence to Katharina Machura.

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Machura, K., Neubauer, B., Müller, H. et al. Connexin 40 is dispensable for vascular renin cell recruitment but is indispensable for vascular baroreceptor control of renin secretion. Pflugers Arch - Eur J Physiol 467, 1825–1834 (2015). https://doi.org/10.1007/s00424-014-1615-y

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  • DOI: https://doi.org/10.1007/s00424-014-1615-y

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