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Role of endothelin-1 for the regulation of renal pelvic function

  • Organ physiology
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Abstract

Endothelin-1 (ET-1) stimulates contractions in isolated rat renal pelves. The signal transduction mechanisms that mediate ET-1-induced renal pelvic contractions and the role of ET-1 for the in vivo regulation of renal pelvic function are not well characterized. We tested if ET-1 stimulates contractions in murine and human renal pelves, if ET-1 activates the renal pelvic RhoA/ROCK pathway, and if low renal ET-1 formation or ET receptor blockade reduce renal pelvic contractile activity. ET-1 increased contraction frequency and force in murine renal pelves. The majority of human renal pelvic tissue samples showed tonic contractions in response to ET-1. Seven out of 20 human tissue samples showed phasic contractions. In four samples, they were elicited by ET-1 at 10–33 nmol/l. ET-1 increased renal pelvic RhoA-GTP content and myosin phosphatase target subunit 1 phosphorylation in isolated rat renal pelves. Renal pelvic contraction frequency (29 ± 2 vs. 29 ± 3 min−1) and renal pelvic pressure (7.1 ± 0.9 vs. 5.9 ± 1.7 mmHg) were similar in collecting duct-specific ET-1 knockout mice and in ET-1 floxed controls in vivo. ET-1 sensitivity of isolated renal pelves was similar in both groups. ET receptor blockade did not significantly affect pelvic contraction frequency and pressure in rats. We conclude that ET-1 stimulates phasic contractions in murine, rat, and, to a lesser extent, in human renal pelves. ET-1 activates the RhoA/ROCK pathway in the renal pelvic wall. Endogenous, kidney-derived ET-1 does not play a major role for the regulation of renal pelvic contractions in vivo.

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Authors and Affiliations

  1. Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany

    Antje Steinbach, Katrin Schaper, Anna Koenen, Torsten Schlüter, Rainer Rettig & Olaf Grisk

  2. Department of Urology, University of Greifswald, Karlsburg, Germany

    Uwe Zimmermann

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  1. Antje Steinbach
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  2. Katrin Schaper
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  3. Anna Koenen
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  7. Olaf Grisk
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Correspondence to Olaf Grisk.

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Steinbach, A., Schaper, K., Koenen, A. et al. Role of endothelin-1 for the regulation of renal pelvic function. Pflugers Arch - Eur J Physiol 468, 1467–1478 (2016). https://doi.org/10.1007/s00424-016-1848-z

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