RENAL DOPAMINE-RECEPTOR FUNCTION IN HYPERTENSION

Dopamine plays an important role in the regulation of renal sodium exc retion. The synthesis of dopamine and the presence of dopamine recepto r subtypes (D-1A, D-1B as D-1-like and D-2, and D-3 as D-2-like) have been shown within the kidney. The activation of D-1-like receptors loc ated on the proximal tubules causes inhibition of tubular sodium reabs orption by inhibiting Na,H-exchanger and Na,K-ATPase activity. The D-1 -like receptors are linked to the multiple cellular signaling systems (namely, adenylyl cyclase, phospholipase C, and phospholipase A(2)) in the different regions of the nephron. Defective renal dopamine produc tion and/or dopamine receptor function have been reported in human pri mary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D-1-like receptors and an altered si gnaling system in the proximal tubules that lead to reduced dopamine-m ediated effects on renal sodium excretion in hypertension. Recently, i t has been shown in animal models that the disruption of either D-1A o r D-3 receptors at the gene level causes hypertension in mice. Dopamin e and dopamine receptor agonists also provide therapeutic potential in treatment of various cardiovascular pathological conditions, includin g hypertension. However, because of the poor bioavailability of the cu rrently available compounds, the use of D-1-like agonists is limited t o the management of patients with severe hypertension when a rapid red uction of blood pressure is clinically indicated and in acute manageme nt of patients with heart failure. in conclusion, there is convincing evidence that dopamine and dopamine receptors play an important role i n regulation of renal function, suggesting that a defective dopamine r eceptor/signaling system may contribute to the development and mainten ance of hypertension. Further studies need to be directed toward estab lishing 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 dopam ine receptor gene causing the hypertension.