762 ACTIVATION OF D4 DOPAMINE RECEPTOR DECREASES AT1 ANGIOTENSIN II RECEPTOR EXPRESSION IN RAT RENAL PROXIMAL TUBULE CELLS

Abstract

Background: The dopaminergic and renin angiotensin systems interact to regulate blood pressure.Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal AT1 receptor expression. We hypothesize that D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubules (RPTs) cells from Wistar-Kyoto (WKY) rats, the regulation of D4 receptor on AT1 receptor is aberrant in RPT cells from spontaneously hypertensive rats (SHRs). Methods And Results: The D4 receptor agonist, PD168077, decreasedAT1 receptor protein expression in WKY RPT cells but increased the receptor expression in SHR RPT cells. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY RPT cells was blocked by a calcium channel blocker, nicardipine or calcium free medium.Angiotensin II increased Na+-K+ ATPase activity in WKY cells.Pretreatment with PD168077decreased the stimulatory effects of angiotensin II on Na+-K+ ATPase activity in WKY cells. However, in SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated Na+-K+ ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na+-K+ ATPase activity in SHR cells. We also infused angiotensin II via renal artery, found sodium excretion decrease, while in the pre-infusion with PD168077, the inhibitory effect of Ang II on sodium excretion was decreased in WKY rats, increased in SHRs. Conclusions: We suggest that a differential interaction between D4 and AT1 receptors may play a role in the differential regulation of sodium excretion and blood pressure in hypertension.