Renal proximal tubular reabsorption is reduced in adult spontaneously hypertensive rats: roles of superoxide and Na+/H+ exchanger 3.

Proximal tubule reabsorption is regulated by systemic and intrinsic mechanisms, including locally produced autocoids. Superoxide, produced by NADPH oxidase enhances NaCl transport in the loop of Henle and the collecting duct, but its role in the proximal tubule is unclear. We measured proximal tubule fluid reabsorption (Jv) in WKY rats and compared that with Jv in the spontaneously hypertensive rat (SHR), a model of enhanced renal superoxide generation. Rats were treated with the NADPH oxidase inhibitor apocynin (Apo) or with small interfering RNA for p22(phox), which is the critical subunit of NADPH oxidase. Jv was lower in SHR compared with Wistar-Kyoto rats (WKY; WKY: 2.3+/-0.3 vs SHR: 1.1+/-0.2 nL/min per millimeter; n=9 to 11; P<0.001). Apo and small interfering RNA to p22(phox) normalized Jv in SHRs but had no effect in WKY rats. Jv was reduced in proximal tubules perfused with S-1611, a highly selective inhibitor of the Na(+)/H(+) exchanger 3, the major Na(+) uptake pathway in the proximal tubule, in WKY rats but not in SHRs. Pretreatment with Apo restored an effect of S-1611 to reduce Jv in the SHRs (SHR+Apo: 2.9+/-0.4 vs SHR+Apo+S-1611: 1.0+/-0.3 nL/min per millimeter; P<0.001). However, because expression of the Na(+)/H(+) exchanger 3 was similar between SHR and WKY rats, this suggests that superoxide affects Na(+)/H(+) exchanger 3 activity. Direct microperfusion of Tempol or Apo into the proximal tubule also restored Jv in SHRs. In conclusion, superoxide generated by NADPH oxidase inhibits proximal tubule fluid reabsorption in SHRs. This finding implies that proximal tubule fluid reabsorption is regulated by redox balance, which may have profound effects on ion and fluid homeostasis in the hypertensive kidney.

Apelin expression in normal human tissues.

Apelin is an endogenous ligand of the human orphan receptor APJ (orphan G protein-coupled receptor). This peptide is produced through processing from the C-terminal portion in the pre-proprotein consisting of 77 amino acid residues and exists in multiple molecular forms. Although the main physiological functions of apelin have not been clarified yet, it has been demonstrated that apelin partially suppresses cytokine production from mouse spleen and, specifically, induces the promotion of extracellular acidification and inhibition of cAMP production in Chinese hamster ovary cells. Moreover, it is involved in the regulation of blood pressure and blood flow. In this study we have analyzed, by immunohistochemistry, apelin distribution in several human tissues, demonstrating that apelin has a widespread pattern of expression. These results seem to confirm that apelin functions widely in various tissues interacting with its specific receptor APJ.