Dopamine plays an important role in the regulation of renal
sodium excretion. The synthesis of
dopamine and the presence of
dopamine receptor subtypes (D1A, D1B, as D1-like and D2, and D3 as D2-like) have been shown within the kidney. The activation of D1-like receptors located on the proximal tubules causes inhibition of tubular
sodium reabsorption by inhibiting
Na,H-exchanger and Na,K-
ATPase activity. The D1-like receptors are linked to the multiple cellular signaling systems (namely,
adenylyl cyclase,
phospholipase C, and
phospholipase A2) in the different regions of the nephron. Defective renal
dopamine production and/or
dopamine receptor function have been reported in human
primary hypertension as well as in genetic models of animal
hypertension. There may be a primary defect in D1-like receptors and an altered signaling system in the proximal tubules that lead to reduced
dopamine-mediated effects on renal
sodium excretion in
hypertension. Recently, it has been shown in animal models that the disruption of either D1A or D3 receptors at the gene level causes
hypertension in mice.
Dopamine and
dopamine receptor agonists also provide therapeutic potential in treatment of various cardiovascular pathological conditions, including
hypertension. However, because of the poor bioavailability of the currently available compounds, the use of D1-like agonists is limited to the management of patients with severe
hypertension when a rapid reduction of blood pressure is clinically indicated and in acute management of patients with
heart failure. In conclusion, there is convincing evidence that
dopamine and
dopamine receptors play an important role in regulation of renal function, suggesting that a defective
dopamine receptor/signaling system may contribute to the development and maintenance of
hypertension. Further studies need to be directed toward establishing a direct correlation between defective
dopamine receptor gene in the kidney and development of
hypertension. Subsequently, it may be possible to use a therapeutic approach to correct the defect in
dopamine receptor gene causing the
hypertension.