Mechanism of action

In common with all catecholamines, dopamine acts on different receptors in a diverse dose-related fashion. Dopamine receptors are present in various sites in the body and have been classified into five subtypes. The two most important receptors in the peripheral cardiovascular and renal systems are DAj and DA2.

The infusion of relatively low concentrations of dopamine activates postsynaptic DAj receptors in blood vessels and the renal tubules. Stimulation leads to vasodilatation and improves some measures of renal function, such as cortical renal blood flow, glomerular filtration rate (GFR), sodium excretion and urine output. There is also an increase in mesenteric flow. Activation of presynaptic DA2 receptors decreases intrarenal norepinephrine release, which leads to vasodilatation. It also causes inhibition of aldosterone secretion from the adrenal glands and a consequent decrease in sodium reabsorption. Theoretically, this should decrease renal oxygen consumption and improve the renal oxygen supply/demand relationship.

Dopamine stimulates its receptors in the renal and splanchnic beds at low infusion rates (0.1-2 pg kg~l min~l). This effect is accompanied by little change in cardiac output or heart rate. A reduction in arterial pressure may occur because of inhibition of the sympathetic nervous system by stimulation of the DA2 receptors, and by DA^-induced vasodilatation.

Increased infusion (2-5 pg kg~l min~l) stimulates Pj- and p2" adrenergic receptors, which causes an increase in myocardial contractility, stroke volume and cardiac output. At this infusion rate, the heart rate usually does not change.

Higher doses of dopamine (> 10 pg kg~l min~l) lead to stimulation of the a-adrenergic receptors, causing vasoconstriction, an increase in peripheral vascular resistance and a decrease in renal and splanchnic blood flow.

The dopamine infusion rates given above are guidelines and there is considerable intra- and inter-patient variation. The maximum dose at which dopamine affects only dopamine receptors is debatable and must be individually determined. Because of the up- and downregulation of receptors, in any one patient, the appropriate dose for a required effect may vary from hour to hour.

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