Dopamine: a role in the pathogenesis and treatment of hypertension

Abstract

The catecholamine dopamine (DA), activates two distinct classes of DA-specific receptors in the cardiovascular system and kidney—each capable of influencing systemic blood pressure. D₁ receptors on vascular smooth muscle cells mediate vasodilation, while on renal tubular cells they modulate sodium excretion. D₂ receptors on pre-synaptic nerve terminals influence noradrenaline release and, consequently, heart rate and vascular resistance. Activation of both, by low dose DA lowers blood pressure. While DA also binds to alpha- and beta-adrenoceptors, selective agonists at both DA receptor classes have been studied in the treatment of hypertension. An unfavourable side-effect profile (largely nausea and orthostasis) have precluded wide use of D₂ agonists. In contrast, the D₁ selective agonist fenoldopam has been licensed for the parenteral treatment of severe hypertension. Apart from inducing systemic vasodilation it induces a diuresis and natriuresis, enhanced renal blood flow, and a small increment in glomerular filtration rate. Evidence is emerging that abnormalities in DA production, or in signal transduction of the D₁ receptor in renal proximal tubules, may result in salt retention and high blood pressure in some humans and in several animal models of hypertension.