Impaired angiotensin II AT < inf > 1 < /inf > receptor function and enhanced Na, K-ATPase affinity for sodium in proximal tubule of streptozotocin-treated diabetic rats

Abstract

We determined angiotensin II (Ang II) AT1 receptor function in terms of Na-K-ATPAse (NKA) stimulation in the proximal tubule (PTs) of streptozotocin-induced diabetic rats. Ang II (10 pM) stimulated NKA activity in PTs of control rats but not diabetic rats. The AT1 receptor expression was similar, but the expression of G-proteins (Giα2 and Giα3) in the PTs was decreased in diabetic compared with control rats. Kinetic studies revealed an increase in NKA affinity, low K0.5, for Na, with no changes in Vmax of the enzyme in diabetic compared with control rats. Basal Ser-phosphorylation of NKA α1-subunit was lower in diabetic compared with control rats. This data suggest that the higher basal NKA affinity for Na, possibly due to lower Ser-phosphorylaion of α1-subunit and not the AT1 receptor function, in the PTs may be responsible for increased renal Na reabsorption associated with early stage of streptozotocin-induced diabetes. Copyright © Informa Healthcare USA, Inc.