Mechanism of sodium load-induced hypertension in non-insulin dependent diabetes mellitus model rats: Defective dopaminergic system to inhibit Na-K-ATPase activity in renal epithelial cells

Obesity-related non-insulin dependent diabetes mellitus (NIDDM) is frequent ly accompanied by hypertension. The present study was designed to clarify t his mechanism. We first determined the blood pressure in male Wistar fatty rats (WFR), one of the NIDDM model rats, and in Wistar lean rats (WLR) as t he control, with a normal(0.7% NaCl) or high (7% NaCl) salt diet. We observ ed no difference in systolic and mean blood pressures between WFR and WLR, WFR, however, became extremely hypertensive as a result of ingesting the hi gh salt diet. We next investigated the mechanism for sodium sensitivity in WFR, Although the urinary excretion of dopamine (DA), a potent natriuretic factor, which reflects the ability for renal DA production, was preserved i n WFR, the sodium balance with the high salt diet was positive. Moreover, N a-K-ATPase activity in isolated proximal convoluted tubules (PCT) from WFR with a normal salt diet was significantly (p<0.05) higher than that from WL R, A high salt load produced a significant (p<0.05) decrease in Na-K-ATPase activity in WLR but not in WFR, Similarly, Na-K-ATPase activity in WLR wit h a normal salt diet was significantly (p<0.05) inhibited by DA (10(-5) M), but this was not true in WFR. Furthermore, urinary excretion of norepineph rine in WFR with a high salt diet was the highest among all the groups. The se results indicate that WFR tend to develop salt-sensitive hypertension th at could be caused by the excessive sodium retention occurring as the resul ts of a defective dopaminergic system in the kidney that fails to inhibit N a-K-ATPase activity. Augmentation of the renal sympathetic nervous system m ay play some role in this setting.