APOPTOSIS ASOCIADA A LA EXPRESIÓN DEL INTERCAMBIADOR Na+/H+ EN OBSTRUCCION RENAL NEONATAL.

WALTER MANUCHA

Merlo - San Luis - Argentina

Congreso; XXII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2004

Sociedad de Biología de Cuyo y Sociedad Argentina de MIcroscopía

The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by epithelial cell apoptosis leading to renal atrophy and tissue loss. Molecular events involved in apoptosis induction have not been complete elucidated yet. Factors as mechanical stretch, Angiotensin II, TGF, oxidative stress and endogenous nitric oxide (NO) have been involved in apoptosis activation. In contrast, epithelial cells expand intracellular volume involving increased expression of the exchanger Na+/H+ (NHE1). The participation of NHE1 in the apoptosis induction was studied, in an experimental model of increased intraluminal hydrostatic pressure, neonatal UUO. Newbom rats were subjected to UUO (n=l0) within the first 48 hours. After 5 and 14 days, the kidneys were removed. Apoptotic cells were identified with TUNEL technique. Morphometric evaluation was performed by Masson Tricrome method. Expression of angiotensin II receptors, TGF, iNOS and Bax/BcL2 were measured by RT-PCR. Decreased expression of AT2 receptor was demonstrated 14 days and 5 days after relief (OC) vs. control (CC): 0.497±0.2 vs 0.993±0.5 (p<0.01) and 0.566±0.3 vs. 0.974±0.3 (p<0.01) respectively. Increased number of apoptotic cells in cortical collecting ducts (CCD) and proximal tubules (PT) in OK related to CK, and near two fold increase Bax/BcL2 ratio after 14 days of obstruction were shown. Decreased iNOS mRNA expression was shown in OK vs. CK (p<0.0l). Slight increase of tubular apoptotic cells in OK and Bax/BcL2 ratio with simultaneous increase in iNOS mRNA expression related to control: 1.253±0.07 vs. 0.767±0.08 (p<0.0l) were shown after 5 days of obstruction. Increased TGF expression was shown after 14 days. Decreased mRNA and protein NHE1 expression in the presence of an intense apoptotic_response allow us to suggest the contribution of this exchanger to intracellular acidosis involved in the apoptotic process.