Activation of angiotensin II type 1 receptors increases D 4 dopamine receptor expression in rat renal proximal tubule cells

Both the dopaminergic and renin–angiotensin systems play important roles in the regulation of blood pressure. Our previous study showed that the stimulation of dopaminergic D 4 receptors reduced angiotensin II type 1 (AT 1 ) receptor expression in renal proximal tubule (RPT) cells. In this study, we tested whether AT 1 receptors, in return, would regulate D 4 receptor expression and function in RPT cells. Expression of the D 4 receptor from Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHRs) RPT cells and renal cortex tissues were determined by western blot, and Na + –K + ATPase activity was determined using an enzyme assay. Urine volume and urine sodium of WKY rats and SHRs treated with or without D 4 receptor stimulation were measured. Thus, activation of AT 1 receptors with angiotensin II (Ang II) increased D 4 receptor protein expression in RPT cells, and this increase was blocked by nicardipine, a calcium influx blocker. The D 4 receptor agonist PD168077 inhibited Na + –K + ATPase activity in WKY RPT cells but not in SHR RPT cells. Ang II pre-treatment promoted D 4 receptor-mediated inhibition of Na + –K + ATPase in RPT cells in WKY rats but not in SHRs. Meanwhile, Ang II pre-treatment augmented the natriuretic effect of PD168077 in WKY rats but not in SHRs. In conclusion, AT 1 stimulation can regulate the expression and natriuretic function of dopaminergic D 4 receptors in RPT cells and might be involved in the pathogenesis of essential hypertension.