Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D1 receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D1 receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.
Since the discovery in 1964 that dopamine produces natriuresis and diuresis (12), a tremendous amount of progress has been made in understanding dopamine-mediated effects on renal and cardiovascular function
Dopamine Deficiency in Human Hypertension.
Deficiency in renal dopamine synthesis and/or secretion has been reported in various forms of human hypertension. Urinary dopamine excretion is lower in salt-sensitive hypertensive patients than in normal subjects or non-salt-sensitive patients on high sodium intake . Suppressed dopaminergic activity has also been shown in the prehypertensive stage of primary hypertension . Reduced dopaminergic activity has also been observed in young normotensive subjects with an apparent family history of hypertension before any evidence of hypertension emerged . The exact mechanism for the renal dopaminergic deficiency in the human primary hypertension is not known. However, a defect in L-dopa-decarboxylase, the enzyme that catalyzes the conversion of L-dopa to dopamine, has been reported in a subject with a family history of hypertension . Other studies have shown a decrease in both the renal tubular uptake of L-dopa and the conversion of L-dopa to dopamine in a subgroup of salt-sensitive hypertensive patients . Because the suppression of renal dopaminergic activity has been observed in young normotensives with a family history of hypertension before any manifestation of the disease, it has been suggested that renal dopaminergic deficiency may contribute to the development of hypertension