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Role of renal innervation and endothelin‐1 for the regulation of upper urinary tract contractions
Author(s) -
Grisk Olaf,
Schaper Katrin,
Steinbach Antje,
Schlüter Torsten,
Zimmermann Uwe,
Rettig Rainer
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.698.1
Subject(s) - rhoa , endocrinology , contraction (grammar) , medicine , endothelin receptor , chemistry , in vivo , endothelin 1 , rho associated protein kinase , transplantation , denervation , kidney , biology , kinase , signal transduction , receptor , biochemistry , microbiology and biotechnology
Contractions of isolated rodent upper urinary tract (UUT) can be stimulated by norepinephrine (NE) and endothelin‐1 (ET‐1) and are sensitive to Rho kinase (ROCK) inhibition. We tested (1.) if renal nerves or paracrine acting ET‐1 are physiological regulators of UUT contractions, (2.) if the RhoA/ROCK pathway mediates NE‐ or ET‐1‐induced UUT contractions, and (3.) if NE or ET‐1 stimulate contractions in human UUT. Renal nerves were removed by kidney transplantation or unilateral denervation in rats. Collecting duct (CD)‐specific ET‐1 k.o. mice served as a model with low renal ET‐1. In vivo, UUT contraction frequency was similar in denervated and control kidneys. In vitro, denervated rat UUTs had a significantly higher spontaneous contraction frequency than controls but did not show NE or ET‐1 supersensitivity. UUTs of CD‐specific ET‐1 k.o. mice and their controls showed similar in vivo and in vitro contractile activity, NE and ET‐1 sensitivity. RhoA GTP formation and MYPT1 phosphorylation was stimulated by ET‐1 but not by NE in rat UUTs. NE and ET‐1 elicited rhythmic and tonic contractions in isolated human UUT tissue. We conclude that renal innervation regulates UUT pacemaker activity and that the RhoA/ROCK pathway mediates ET‐1‐induced UUT contractions. We suggest that rodent data on UUT function can be at least in part translated to humans.