16 October 2007
Background/Aims: The renal sodium glucose cotransporter (SGLT2) and the water channel aquaporin-2 (AQP2) play a critical role in tubular sodium and water reabsorption and in the regulation of extracellular fluid volume both in physiologic and pathophysiologic conditions. However, there is little information about SGLT2 and AQP2 expression and/or activity in hypertension and there are no reports during hypertension induced by chronic nitric oxide synthase (NOS) inhibition. Methods: Hypertension was induced in rats by oral administration of N<sup>G</sup>-nitro- L-arginine methyl ester ( L-NAME) (20 mg/kg/24 h) for 6 (H6) or 12 (H12) weeks. SGLT2 activity was measured using α-<sup>14</sup>C-methylglucose active uptake. The expression level of transporters was assessed by immunohistochemistry and/or immunoblotting. Results: SGLT2 activity was reduced in both H6 and H12; this was due neither to a decrease in SGLT2 expression nor to a change in membrane phospholipid composition. In H6, AQP2 expression diminished only in the inner medulla (IM), while in H12 it diminished in both outer (OM) and IM. This reduced expression of AQP2 may partially account for the increased urinary volume and decreased urinary osmolality in H12, since we obtained a strong correlation between AQP2 expression and these urinary parameters in both OM and IM. Conclusion: We propose that in rats in which hypertension is induced by NOS inhibition, SGLT2 activity and AQP2 expression are modified to compensate for the elevated arterial pressure. However, we cannot discount the possibility that the observed changes are due to the decrease in NO production itself.