DOPAMINE REGULATION OF RENAL NA-ATPASE ACTIVITY IS LACKING IN DAHL SALT-SENSITIVE RATS(,K+)

Dopamine is a natriuretic hormone that acts by inhibiting tubular Na+, K+-ATPase activity by activation of the dopamine-1 receptor (the thick ascending limb [TAL] of Henle) or by a synergistic effect of dopamine -1 and dopamine-2 receptors (the proximal tubule). The dopamine-1 rece ptor is coupled to adenylate cyclase. In this article we show that pre hypertensive Dahl salt-sensitive (DS) rats have a blunted natriuretic response to dopamine determined during euvolemic conditions compared w ith Dahl salt-resistant (DR) rats. Furthermore, we have examined the r enal tubular effects of dopamine in DS and DR rats. Basal Na+,K+-ATPas e activity was similar in DS and DR rats. In proximal tubule, dopamine (10(-5) M) inhibited Na+,K+-ATPase activity in DR but not in DS rats. The dopamine-2 agonist LY171555 (10(-5) M) together with dibutyryl cy clic AMP (10(-6) M) inhibited proximal tubule Na+,K+-ATPase activity i n both DS and DR rats. LY171555 alone had no effect. In TAL, the dopam ine-1 agonist fenoldopam (10(-5) M) inhibited Na+,K+-ATPase activity i n DR but not in DS rats. Dibutyryl cyclic AMP (10(-5) M) inhibited TAL Na+,K+-ATPase activity in both DS and DR rats. In cell suspensions fr om the cortex and the medulla, activation of the dopamine-1 receptor s ignificantly increased cyclic AMP content in DP but not in DS rats. Th e results indicate that DS rats lack the capacity to inhibit tubular N a+,K+-ATPase activity because of a defective dopamine-1 receptor adeny late cyclase coupling. This defect may contribute to the impaired natr iuretic capacity in DS rats.