Angiotensin receptor-1A knockout leads to hydronephrosis not associated with a loss of pyeloureteric peristalsis in the mouse renal pelvis

The action of angiotensin II (AngII) on the Ca²⁺ signals driving pyeloureteric peristalsis was investigated using both conventional and angiotensin receptor (ATr) ATr1A and ATr2 knockout (^−/−) mice. Contractility in the renal pelvis of adult ATr1A^−/− and ATr2^−/− mice was compared to their respective wildtype (ATr1A^+/+ and ATr2^+/+) controls of the same genetic background (FVB/N and C57Bl/6 respectively) using video microscopy. The effects of AngII on the Ca²⁺ signals in typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) within the pelvic wall of conventional mice were recorded using Fluo-4 Ca²⁺ imaging. Compared to ATr1A^+/+, ATr2^+/+ and ATr2^−/− mice, kidneys of the ATr1A^−/− mouse were mildly-to-severely hydronephrotic, associated with an enlarged calyx, an atrophic papilla and a hypoplastic renal pelvis. Contraction frequencies in the renal pelvis of moderately hydronephrotic ATr1A^−/− and unaffected ATr2^−/− mice were not significantly different from their ATr1A^+/+, ATr2^+/+ controls. No contractions were observed in severely-hydronephrotic ATr1A^−/− kidneys. AngII increased the spontaneous contraction frequency of the renal pelvis in ATr1A^+/+, ATr2^+/+ and ATr2^−/− mice, but had little effect on the contractions in the mildly-hydronephrotic ATr1A^−/− renal pelvis. The ATr1 blocker, candesartan prevented the positive chronotropic effects of AngII. AngII increased the frequency and synchronicity of Ca²⁺ transients in both TSMCs and ASMCs. It was concluded that the hydronephrosis observed in ATr1A^−/− mouse kidneys does not arise from a failure in the development of the essential pacemaker and contractile machinery driving pyeloureteric peristalsis.