UNILATERAL URETERAL OBSTRUCTION: MARKERS OF EARLY FIBROGENESIS IN NEONATAL RATS

WALTER MANUCHA; LILIANA CARRIZO; PATRICIA G. VALLES

Mendoza - Argentina

Congreso; XXI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2003

Sociedad de Biología de Cuyo y Sociedad Argentina de Microscopía

Unilateral ureteral obstruction (UUO) is characterized by tubular atrophy, increased interstitial fibroblasts and mononuc!ear cells. It is initiated by alterations of intrarenal angiotensin II, inflamma­tory cytokines and nitric oxide. Mechanical factors induce changes in cell volumen resulting in tubular atrophy. Regulatory volume increase in tubular epithelial is achieved by activation of the Na/H exchanger isoform 1 (NHE1). We evaluated markers of early fíbrogenesis in neonatal rats (NEO) with UUO and compared them with. adult rats. Experimental model:  48 h after birth, UUO was performed. Nephrectomy was done after 5 days. RT-PCR mRNA was measured (AT1, AT2, TGF and NHE1) Interstilial volume and tubular diameters were evaluated staining renal sections with Masson trichrome. AT2 angiotensin II receptors showed increased expres­sion in cortex kidney of NEO vs control (0.946±0.05 vs 0.69±0.06 p< 0.01) without difference in AT1, receptor expression. On the contrary, adult rats had decreased AT1 receptor expression without changes in AT1 receptor. TGF expression was increased in NEO (0.936±0.07 vs 0.683±0.05 p<0.01) and in adult rats (0.750±0.05 vs 0.637±0.04 p<0.05). NEO cortex NHE1 expression was increased (0.957±0.04 vs 0.683±0.03, p< 0.01). Atrophy, as­sessed by proximal and cortical collecting dut diameter, was in­creased jn NEO (26.77±3.66 vs 9.25±1.23, p<0.01) There was no.change in adult rats tubular diameter. Interstitial volume was in­creased in adult rats (13.7±1.5 vs 28±2.6 p<0.01), but not in NEO. Our results suggest that fíbrogenesis in NEO obstructed kid­neys inc1udes an intense ear1y damage of proximal and cortical collecting duct segments resulting in tubular atrophy.