Renal dopaminergic mechanisms and hypertension: A chronology of advances

Dopamine (DA) has been shown to influence kidney function through endogenou s synthesis and subsequent interaction with locally expressed dopamine rece ptor subtypes (D-1, D-5 as D-1 -like and D-2, D-3, and D-4 as D-2 -like). D A, and DA-receptor specific agonists and antagonists can alter renal water and electrolyte excretion along with renin release when infused systemicall y or intrarenally. Such effects ale brought about by a combination of renal hemodynamic and direct tubular effects evoked along the full length of the nephron. The cellular mechanisms that direct these dopamine-mediated renal electrolyte fluxes have recently been clarified and include alterations in adenylyl cyclase, phospholipase C, and phospholipase A(1) activity. The do paminergic system also interacts directly with the renal kallikrein-kinin, prostaglandin and other neurohumoral systems. Aberrant renal dopamine produ ction and/or dopamine receptor function have been reported in salt-dependen t and low-renin forms of human primary hypertension as well as in genetic m odels of animal hypertension, including the SHR and Dahl SS rat. DA D-1 or D-3 receptor knockout mice have been shown to develop hypertension.