Role of dopamine in the pathogenesis of hypertension

1. Dopamine, via different dopamine receptor subtypes, regulates cardiovascular functions by actions on the central and peripheral nervous systems, vascular smooth muscle, the heart and the kidney. The dopaminergic system in the central nervous system (CNS) may participate in the regulation of systemic blood pressure. 2. Dopamine 'D2-like' (D2, D3 and D4) receptors, rather than 'D1-like' (D1 and D5) receptors, are involved in the CNS regulation of blood pressure; post-synaptic D2-like receptors increase blood pressure, while presynaptic D2-like receptors (the predominant action) produce the opposite effect. 3. Outside the CNS, dopamine may regulate blood pressure via pressure controls that act with intermediate rapidity (e.g. stress relaxation, arginine vasopressin and renin-angiotensin vasoconstriction), as well as those systems related to the long-term control of body fluid volume. 4. Dopamine D1- and D2-like receptors have been described in resistance vessels, such as the renal, mesenteric, coronary, pulmonary and cerebral arteries. The ability of D1-like receptors to inhibit renal smooth muscle hypertrophy indicates their importance in longer-term regulation of blood pressure. 5. Aberrant dopaminergic regulation of aldosterone secretion, via D2-like receptors, has been reported to be involved in some forms of hyperaldosteronism and hypertension. Some forms of hypertension may also be caused by an aberrant renal dopaminergic system. Abnormalities of three aspects of the renal dopaminergic system may lead to hypertension: (i) renal production of dopamine; (ii) transduction of the renal vascular dopamine signal; and (iii) transduction of the renal tubular dopamine signal. 6. Thus, increased blood pressure occurs after either blockade of D1-like receptors or of dopamine production in rats or disruption of the D1 receptor or the D3 receptor gene in mice.