Abstract
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.
Original language | English |
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Pages (from-to) | 535-542 |
Number of pages | 8 |
Journal | Clinical and Experimental Pharmacology and Physiology |
Volume | 43 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2016 |
Keywords
- angiotension II
- Ca2+ signalling
- pacemaker cells
- pyeloureteric peristalsis
- smooth muscle
- upper urinary tract