Role of endothelin-1 for the regulation of renal pelvic function.
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.
Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany.
Antje
A
Steinbach
Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany.
Katrin
K
Schaper
Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany.
Anna
A
Koenen
Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany.
Torsten
T
Schlüter
Department of Urology, University of Greifswald, Karlsburg, Germany.
Uwe
U
Zimmermann
Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany.
Rainer
R
Rettig
Department of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany. grisko@uni-greifswald.de.
Olaf
0000-0001-6842-1256
O
Grisk
D000368:Aged; D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007682:Kidney Pelvis / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D019332:Endothelin-1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
Animals; Endothelin-1; Humans; Rho kinase; Upper urinary tract