Renal Dopamine System Paracrine Regulator of Sodium Homeostasis and Blood Pressure

All of the components of a complete dopamine system are present within the kidney, where dopamine acts as a paracrine substance in the control of sodium excretion. Dopamine receptors can be divided into D1-like (D1 and D5) receptors that stimulate adenylyl cyclase and D2-like (D2, D3, and D4) receptors that inhibit adenylyl cyclase. All 5 receptor subtypes are expressed in the kidney, albeit in low copy. Dopamine is synthesized extraneuronally in proximal tubule cells, exported from these cells largely into the tubule lumen, and interacts with D1-like receptors to inhibit the Na-H exchanger and Na,K-ATPase, decreasing tubule sodium reabsorption. During moderate sodium surfeit, dopamine tone at D1-like receptors accounts for '50% of sodium excretion. In experimental and human hypertension, 2 renal dopaminergic defects have been described: (1) decreased renal generation of dopamine and (2) a D1 receptor–G protein coupling defect. Both defects lead to renal sodium retention, and each may play an important role in the pathophysiology of essential hypertension. (Hypertension. 2001;38:297-302.)