Differential regulation of Na+,K+-ATPase and the Na+-coupled glucose transporter in hypertensive rat kidney

Several Na⁺ transporters are functionally abnormal in the hypertensive rat. Here, we examined the effects of a high-salt load on renal Na⁺,K⁺-ATPase and the sodium-coupled glucose transporter (SGLT1) in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. The protein levels of Na⁺,K⁺-ATPase and SGLT1 in the DS rat were the same as those in the DR rat, and were not affected by the high-salt load. In the DS rat, a high-salt load decreased Na⁺,K⁺-ATPase activity, and this decrease coincided with a decrease in the apparent Mechaelis constant (K_m) for ATP, but not with a change of maximum velocity (V_max). On the contrary, a high-salt load increased SGLT1 activity in the DS rat, which coincided with an increase in the V_max for α-methyl glucopyranoside. The protein level of phosphorylated tyrosine residues in Na⁺,K⁺-ATPase was decreased by the high-salt load in the DS rat. The amount of phosphorylated serine was not affected by the high-salt load in DR rats, and could not be detected in DS rats. On the other hand, the amount of phosphorylated serine residues in SGLT1 was increased by the high-salt load. However, the phosphorylated tyrosine was the same for all samples. Therefore, we concluded that the high-salt load changes the protein kinase levels in DS rats, and that the regulation of Na⁺,K⁺-ATPase and SGLT1 activity occurs via protein phosphorylation.