Objectives: 

Norepinephrine (NE) and endothelin-1 (ET-1) stimulate contractions of isolated rodent upper urinary tract UUT in a Rho kinase (ROCK)-dependent manner. We tested if renal innervation and paracrine acting ET-1 are physiological regulators of UUT contractile activity and if NE and ET-1 activate the RhoA ROCK pathway in the UUT.

Methods: 

Kidney transplantation or unilateral renal denervation was performed to remove renal nerves. As a model with reduced renal ET-1 content collecting duct-specific ET-1 k.o. mice were investigated. UUT pressure, diuresis and natriuresis were monitored in vivo. Contractions of isolated UUTs were investigated by myography. RhoA and ROCK activation were measured by G-LISA and Western blot.

Results: 

UUT contraction frequency was 27 ± 2/min in denervated and 28 ± 2/min in control kidneys (n.s.). UUT pressure was 4.6 ± 0.6 mmHg in denervated and 1.8 ± 0.7 mmHg in controls (p < 0.05). Ex vivo, denervated UUTs had a higher spontaneous contraction frequency than controls, but did not show NE or ET-1 supersensitivity. Collecting duct-specific ET-1 k.o. mice did not differ from their controls with regard to in vivo and ex vivo UUT contractile activity and ET-1 sensitivity. ET-1 but not NE stimulated RhoA GTP formation and MYPT1 phosphorylation in isolated rat UUTs.

Conclusions: 

Renal innervation contributes to the regulation of UUT pacemaker activity. The lack of endogenous ET-1 in the collecting duct does not affect basic UUT contractile activity. ET-1 but not NE stimulates the RhoA / ROCK pathway in the UUT.