Trapping intracellular ANG II to the proximal tubule: powerful in vivo effects on sodium handling and blood pressure

Abstract

destined for secretion out of the cells, ECFP/ANG II protein is thus trapped within the cytoplasm of the proximal tubule cell and is unable to act on cell surface AT1 receptors. Confirmation of the expression pattern of ECFP/ANG II was performed by fluorescent immunohistochemical localization using CFP- and ANG II-specific antibodies to cortical proximal tubules with limited expression in glomeruli, cortical connecting tubules, and medullary tissues. Ectopic ECFP/ ANG II expression was very low to undetectable in extrarenal tissues. Most interesting was the demonstration of a significantly elevated renal sodium reabsorption and ultimately increased blood pressure in the animals injected with the ECFP/ANG II adenovirus compared with animals injected with the scrambled version of the fusion protein construct. Two weeks following the introduction of the ECFP/ANG II vector, peptide levels of ANG II were significantly increased in the injected kidney and freshly isolated proximal tubules without alterations in the plasma or urinary levels of the peptide, suggesting that the blood pressure effects reflect the intracellular expression of the peptide. These hypertensive effects were observed in both