title: Angiotensin receptor-1A knockout leads to hydronephrosis not associated with a loss of pyeloureteric peristalsis in the mouse renal pelvis.
abstract: The action of angiotensin II (AngII) on the Ca(2+) 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 Ca(2+) signals in typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) within the pelvic wall of conventional mice were recorded using Fluo-4 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nguyen
authors.affiliation: Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
authors.affiliation: Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D005260:Female; D055786:Gene Knockout Techniques; D006869:Hydronephrosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D007682:Kidney Pelvis / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D010528:Peristalsis / Q000187:drug effects / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency* / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency / Q000235:genetics
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II
keywords: Ca2+ signalling; angiotensin II; pacemaker cells; pyeloureteric peristalsis; smooth muscle; upper urinary tract