POTASSIUM-DEPLETION STIMULATES MESSENGER-RNA EXPRESSION OF PROXIMAL TUBULE AT(1) ANGIOTENSIN-II RECEPTORS

Dietary potassium (K+) deficiency is associated with blood pressure el evation and impaired urinary sodium excretion. Since angiotensin II is a potent stimulator of tubular sodium transport, we studied the effec t of low [K+] on expression of kidney AT(1) angiotensin receptors. In rabbits fed a K+-deficient diet for 14 days, plasma [K+] was significa ntly reduced compared to rabbits fed a standard diet (control: 4.06 +/ - 0.12 vs. K+-deficient: 2.66 +/- 0.19 mmol/l; p < 0.001; n = 6-9). By Northern hybridization or RNase protection assays, dietary K+ deficie ncy caused an increase in mRNA expression for AT(1) receptors in kidne y cortex (43.5 +/- 12.9% increase vs. control; p < 0.04; n = 8), and i n proximal tubule segments in suspension (76.4 +/- 28.8% increase vs. control; p < 0.005; n = 6). K+ deficiency had no effect on AT(1) recep tor mRNA expression in liver, or on mRNA expression of beta-actin in k idney cortex, proximal tubule suspensions, or liver. To determine if l ow extracellular [K+] might directly modulate AT(1) receptor mRNA expr ession, primary cultures of rabbit proximal tubule cells were incubate d for 1, 3, 6 or 24 h in media with or without 5 mmol/l K+. Incubation of cells in 0 mmol/l K+ caused a 99.2 +/- 32.9% increase in AT(1) rec eptor mRNA expression at 3 h (p < 0.001; n = 14), returning to control levels by 24 h, Incubation of proximal tubule cells in 0 mmol/l. K+ a lso caused a significant increase in basolateral membrane specific bin ding of [I-125]-angiotensin II (p < 0.05; n = 4). These results indica te that dietary K+ deficiency and low extracellular [K+] stimulate exp ression of kidney AT(1) angiotensin II receptors. Increased AT(1) rece ptor mRNA and protein expression in proximal tubule may promote enhanc ed sodium reabsorption in K+ deficiency.