Caffeine decreases the expression of Na+/K+-ATPase and the type 3 Na+/H+ exchanger in rat kidney.

1. The aim of the present study was to explore the mechanisms underlying the renal effects of caffeine. 2. Male Sprague-Dawley rats were treated with caffeine, consisting of a single oral bolus (0.2%, 20 mL/kg) followed by supplementation in drinking water (0.2%) for 1 day. Rats treated the same but given water without caffeine served as controls. 3. The expression of alpha1- and beta1-subunits of Na+/K+-ATPase, the type 3 Na+/H+ exchanger (NHE3) and aquaporin-1 was determined in the kidney by western blot analysis. 4. To explore possible involvement of local humoral mediators, the tissue expression of nitric oxide synthase (NOS) proteins was determined by western blot analysis and the expression of atrial natriuretic peptide (ANP) mRNA was determined by semiquantitative reverse transcription-polymerase chain reaction. 5. Following treatment with caffeine, the expression of alpha1- and beta1-subunits of Na+/K+-ATPase, as well as that of NHE3, was decreased. Accordingly, the catalytic activity of Na+/K+-ATPase was decreased. In contrast, the expression of aquaporin-1 was not altered significantly. 6. The expression of the endothelial isoform of NOS was increased, along with tissue nitrite/nitrate levels. The expression of ANP mRNA was increased. 7. It is suggested that caffeine decreases Na+/K+-ATPase and NHE3 activities and increases nitric oxide and ANP activities in the kidney.