D3 Dopamine Receptor and Essential Hypertension

Dopamine receptors are expressed in a number of organs and tissues; the peripheral dopamine receptors influence cardiovascular and renal function by decreasing preload and afterload and by regulating fluid and electrolyte transport. Most of the knowledge on these actions of dopamine has been garnered from studies of D1-like dopamine receptors. The D3 dopamine receptor subtype, which belongs to the D2-like receptor subfamily, has been extensively studied in the neurosciences. Recently, the peripheral actions of the D3 receptor have also raised considerable interest. Previous studies showed that the D3 receptor is expressed in organs outside the central nervous system such as the kidneys and blood vessels. Activation of the D3 receptor, alone or in synergism with D1 receptor induces diuresis and natriuresis and dilates resistance vessels. The D3 receptor also interacts positively with endothelin type B receptors and negatively with the renin-angiotensin-aldosterone system. For example, the D3 receptor-mediated natriuresis can be blocked by ETB receptor antagonists and stimulation of the D3 receptor decreases AT1 receptor expression in renal proximal tubule cells and inhibits renin and aldosterone secretion. The high blood pressure observed in spontaneously hypertensive rats and D3 receptor deficient mice, may, in part, be caused by impaired D3 receptor-mediated renal sodium excretion, impaired interaction with D1 and ETB receptors and impaired inhibition of the renin-angiotensin-aldosterone system. In this review, we examine the role of the peripheral D3 receptor in the regulation of renal sodium excretion and vascular resistance, and its interaction with the renin-angiotensin system and other dopamine receptor subtypes. We also present our current understanding of the role of D3 receptor in the pathophysiology of human essential hypertension.