Angiotensin receptor-1A knockout leads to hydronephrosis not associated with a loss of pyeloureteric peristalsis in the mouse renal pelvis
| Autor: | Michael J Nguyen, Richard J Lang, Hikaru Hashitani |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Angiotensin receptor Contraction (grammar) Physiology Myocytes Smooth Muscle Urology Video microscopy Hydronephrosis Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 Contractility 03 medical and health sciences Gene Knockout Techniques Mice 0302 clinical medicine Biological Clocks Physiology (medical) Internal medicine medicine Animals Kidney Pelvis Calcium Signaling Pharmacology Chemistry Angiotensin II medicine.disease Candesartan 030104 developmental biology Endocrinology medicine.anatomical_structure Female Peristalsis Renal pelvis 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Clinical and experimental pharmacologyphysiology. 43(5) |
| ISSN: | 1440-1681 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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