Losartan reverses fibrotic changes in cortical renal tissue induced by ischemia or ischemia-reperfusion without changes in renal function.
Unilateral renal ischemia for 40 min in rat results in increased fibronectin (FN) expression in proximal tubular cells. This study examines the role of 24 h of blood reperfusion and the role of the renin-angiotensin system (RAS) on these results. Rats were submitted to 40 min of unilateral renal ischemia followed by 24 h of blood reperfusion. Renal function was assayed by clearance measurement in metabolic cages. Intracellular ATP and calcium were determined in proximal tubules. The expression and abundance of FN were investigated by reverse transcription-polymerase chain reaction, ELISA and Western blot either in isolated proximal tubules or cortex homogenates from control, ischemic and ischemic with reperfusion rats. Matrix metalloproteases (MMPs) activity was also measured. Losartan effects on renal function and on the abundance of FN and the MMPs activity in cortical homogenates were also measured. The renal function remained altered after 24 h of reperfusion in untreated and losartan-treated ischemic rats. On the other hand, the abundance of FN is increased after reperfusion both in isolated proximal tubules and total cortex homogenates and the same pattern was observed in the MMPs activity. Twenty-four h of blood reperfusion presented FN-mRNA signals similar to control ones. Losartan pretreated-rats presented diminished FN abundance in homogenates of cortex tissue from ischemic rats with or without reperfusion. Similar results were observed in the MMPs-activity. These results suggest that angiotensin II acting via the AT1 receptor plays a role in the development of tubulointersticial fibrosis after ischemia-reperfusion by activation of intrarenal RAS from the injured kidney.
Barrilli
Andrés
A
Farmacología, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Rosario, Santa Fe, Argentina.
Molinas
Sara
S
Petrini
Guillermo
G
Menacho
Mauricio
M
Elías
María Mónica
MM
D000818:Animals; D001806:Blood Urea Nitrogen; D005353:Fibronectins / Q000096:biosynthesis; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D007511:Ischemia / Q000503:physiopathology*; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D012964:Sodium / Q000652:urine; D014867:Water / Q000378:metabolism
D005353:Fibronectins; D014867:Water; D012964:Sodium; D020782:Matrix Metalloproteinases; D019808:Losartan; D011188:Potassium