-Decreased NHE1 linked to apoptosis in neonatal unilateral ureteral obstruction (UUO).Losartan effect

BOCANEGRA MARIA VICTORIA; MANUCHA WALTER; VICENTI AMANDA; FORNES MIGUEL; MANUCHA W, OLIVEROS L, CARRIZO L., SELTZER A, GARRAMUÑO VALLÉS PATRICIA

Mendoza, Argentina

Congreso; XXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo y I Reunión de la Dirección de Investigación, Ciencia y Técnica dependiente del Ministerio de Salud Gobierno de Mendoza.; 2008

Sociedad de Biología de Cuyo

Apoptosis is associated with NHE1 decreased in neonatal obstructive nephropaty. Losartan effect.Bocanegra V; Manucha W; Vincenti A; Fornés MW; Valles P.The RAS plays a central role in renal disorders progression. OUU markedly activates the RAS mechanical signal resulting from OUU increases hydrostatic pressure and tubule dilation which in turn lead to apoptosis. NHE1 is an important regulatory volume increase component. We examined the NHE1 participation in apoptosis and we further evaluated Angiotensin II inhibition effects in neonatal UUO. Within 48h of birth rats were subjected to OUU or sham surgery.They received Losartan, 10mg/kg/d (CLos/OLos); AT2 inhibitor, PD-123319(CPD/OPD), or vehicle (CH2O/OH2O) for 14 days TUNEL, electron microscopy,WesternBlot(NHE1,NHE3, Bax, Bcl2, Procaspase3 and Caspase3)and Caspase3 assay were performed. Increased apoptotic cells in CCD of OH2OvsCH2O with persistence of apoptosis in OLos were shown. Apoptosis was confirmed by electron microscopy. PD123319 had no effect. We demonstrated decreased NHE1 protein expression in OH2O and OLos vs control whereas no differences in NHE3 expression was shown. The increased Bax/Bcl2 ratio linked to decreased Procaspase3 and increased Caspase3 activity demonstrated the activation of the mitochondrial apoptotic pathway in OLos and OH2O cortex.In conclusion, decreased NHE1 expression may be involved in the persistent tubular epithelial cell apoptosis through the mitochondrial pathway after Losartan administration in neonatal UUO. Losartan should be avoided in neonatal obstructive nephropathy.