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

作者：Nguyen Michael J; Hashitani Hikaru; Lang Richard J^*

来源：CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2016, 43(5): 535-542.

DOI：10.1111/1440-1681.12560

• angiotensin II
• Ca2+ signalling
• pacemaker cells
• pyeloureteric peristalsis
• smooth muscle
• upper urinary tract

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 toATr1A(+/+), 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.

• 出版日期2016-5