Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats

Abstract

Introduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats.