Dopamine fails to inhibit renal tubular sodium pump in hypertensive rats.
We have previously reported that dopamine-1 receptor-mediated activation of phospholipase C is diminished in renal cortical slices of adult spontaneously hypertensive rats. To determine the potential consequences of this phenomenon, we performed the present studies in which renal proximal tubule suspensions obtained from spontaneously hypertensive and Wistar-Kyoto rats of 10-12 weeks of age were used. The tubule suspensions were incubated with dopamine in the presence or absence of dopamine receptor antagonists, and sodium, potassium adenosine trisphosphatase (sodium pump) activity was measured as the ouabain-sensitive adenosine trisphosphate hydrolysis. We found that dopamine produced a concentration-related inhibition of sodium pump activity in the normotensive rats but not in the hypertensive rats. Dopamine-induced inhibition of sodium pump activity in the normotensive rats was abolished by the phospholipase C inhibitor U-73122 or the protein kinase C inhibitor sphingosine, suggesting the involvement of a phospholipase C-coupled protein kinase C pathway in this response. Dopamine-induced inhibition in the normotensive rats was attenuated by the dopamine-1 receptor antagonist SCH 23390 but not by the dopamine-2 receptor antagonist domperidone. To identify possible sites of defect in dopamine-1 receptor-coupled signaling pathways in the hypertensive rats, we incubated the proximal tubules with phorbol 12,13-dibutyrate or the synthetic diacylglycerol analogue 1-oleoyl-2-acetyl-rac-glycerol. The results showed that both compounds inhibited sodium pump activity as effectively in the hypertensive as in the normotensive rats, suggesting that the protein kinase C-coupled sodium pump pathway was not defective in the hypertensive animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Houston, TX 77204-5515.
C
C
Chen
R E
RE
Beach
M F
MF
Lokhandwala
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D010738:Type C Phospholipases / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine