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- Title
Angiotensin receptor-1A knockout leads to hydronephrosis not associated with a loss of pyeloureteric peristalsis in the mouse renal pelvis.
- Authors
Nguyen, Michael J; Hashitani, Hikaru; Lang, Richard J
- Abstract
The action of angiotensin II (Ang II) 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 Ang II 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. Ang II 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 Ang II. Ang II 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.
- Subjects
ANGIOTENSIN II; PHYSIOLOGICAL effects of angiotensins; ANGIOTENSIN receptors; HYDRONEPHROSIS; PERISTALSIS; LABORATORY mice; PHYSIOLOGY
- Publication
Clinical & Experimental Pharmacology & Physiology, 2016, Vol 43, Issue 5, p535
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12560