Dopamine-1 receptors in the proximal convoluted tubule of Dahl rats: Defective coupling to adenylate cyclase

We have previously reported a defect in the coupling of the renal dopamine-1 receptor (D₁) to adenylate cyclase (AC) in the proximal convoluted tubule (PCT) of the spontaneously hypertensive rat (Okamoto-Aoki strain). To determine if this defect is present in another model of hypertension, we microdissected PCTs from Dahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats on low- or high-NaCl diet. The ability of two selective D₁ agonists, fenoldopam and SND-919-C12, and forskolin to stimulate AC activity in PCT was determined in each of the four groups of rats. Fenoldopam (10^-7 M) and SND-919-C12 (10^-6 M) failed to stimulate AC activity in the PCT of DSS rats whether on a low- or high-NaCl diet. In DSR rats, however, both fenoldopam and SND-919-C12 stimulated AC activity by 289- 320% and 220-270%, respectively, whether on a low- or high-NaCl intake. Forskolin (10^-5 M), which directly stimulates AC activity, increased AC activity in all four groups. These studies show that in DSS rats the D₁ receptor in the PCT fails to respond to D₁ agonists. This defect is not a consequence of the hypertension because it was present in the DSS rats on a low-salt diet and before blood pressure elevation.