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

Michael J Nguyen, Hikaru Hashitani, Richard J Lang

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)535-542
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume43
Issue number5
DOIs
Publication statusPublished - May 2016

Keywords

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

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