Author + information
- 1Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, P.R. China
- 2Chongqing Institute of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, PR China
- 3Chongqing Cardiovascular Clinical Research Center, Daping Hospital, Third Military Medical University, Chongqing, PR China
Both dopaminergic and renin-angiotensin systems play important roles in regulation of blood pressure. Our previous study showed that stimulation of dopaminergic D4 receptor reduced angiotensin II type 1 (AT1) receptor expression in renal proximal tubule (RPT) cells. In the present study, we test if AT1 receptor in return regulates D4 receptor expression and function in RPT cells.
Expression of D4 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 by using enzyme assay. Urine volume and urine sodium of WKY rats and SHRs treated with or without D4 receptor stimulator were collected.
As a result, activation of AT1 receptor with angiotensin II (Ang II) increased D4 receptor protein expression in RPT cells, which was blocked by calcium influx blocker nicardipine. D4 receptor agonist PD168077 inhibited Na+-K+ ATPase activity in WKY RPT cells but not SHR RPT cells. Ang II pretreatment promoted D4 receptor-mediated inhibition of Na+-K+ ATPase in RPT cells from WKY rats but not SHRs. Meanwhile, Ang II pretreatment augmented the natriuretic effect of PD168077 in WKY rats but not in SHRs.
In conclusion, AT1 stimulation can regulate the expression and natriuretic function of dopaminergic D4 receptor in RPT, which might be involved in the pathogenesis of essential hypertension.