IMPAIRED AQUAPORIN AND UREA TRANSPORTER EXPRESSION IN RATS WITH ADRIAMYCIN-INDUCED NEPHROTIC SYNDROME

Nephrotic syndrome is associated with abnormal regulation of renal wat er excretion. To investigate the role of collecting duct watts channel s and solute transporters in this process, we have carried out semiqua ntitative immunoblotting of kidney tissues from rats dth adriamycin-in duced nephrotic syndrome. These experiments demonstrated that adriamyc in-induced nephrotic syndrome is associated with marked decreases in e xpression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressi n-regulated urea transporter in renal inner medulla, indicative of a s uppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-sub unit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the c ollecting ducts are morphologically normal and unobstructed. Inner med ullary; expression of the descending limb water channel, aquaporin-1. was not significantly altered, pointing to a selective effect on the c ollecting duel. Aquaporin-2 and aquaporin-3 expression was also marked ly diminished in the renal cortex, indicating that the effect is nut l imited tu the inner medullary collecting duct. Differential centrifuga tion studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane , consistent with the expected short-term action of vasopressin an aqu aporin-2 trafficking. The extensive down-regulation of aquaporin and u rea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and d iluting capacity.