Dopamine and the kidney in heart failure.
Dopamine, administered as in intravenous infusion, has shown unique pharmacological properties in the cardiovascular and renal system with respect to the other catecholamines. These properties, which are the basis of its clinical use, have been related to the stimulation not only of beta- and alpha-adrenergic receptors, but of specific dopamine receptors, particularly when dopamine is administered at a low rate of infusion (0.5 to 2 micrograms/kg.min). Peripheral dopamine receptors of the DA1 and DA2 subtype are located in the arterial bed, in prejunctional sympathetic fibres, and probably on specific dopaminergic neurons, and mediate vasodilation either directly or through the control of sympathetic tone. DA1 and DA2 receptors are also located in the kidney and are involved in the control of electrolyte excretion and in renin release; in the adrenal cortex, DA2 receptors exert control on aldosterone release. These findings, and the local synthesis of dopamine in the proximal tubular cells, strongly suggest a physiological role of dopamine in cardiovascular-renal homeostasis in health and disease. Various efforts of expanding and improving the therapeutic use of dopamine have allowed important progress in the understanding of dopaminergic mechanisms in laboratory and clinical pharmacology; the selective DA1 agonist fenoldopam and gludopa, a prodrug delivering dopamine to the kidney, have been particularly useful in this respect. Ibopamine, a prodrug which is able to produce dopamine-like effects on oral administration, has proved its clinical usefulness in the chronic treatment of congestive heart failure, as a monotherapy in mildly affected patient, or in combination therapy in severe patients. In the light of these, and other, results the importance of further effort in pathophysiological and therapeutic research in this field has to be emphasized.
Casagrande
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Simes Cardiovascular Research Centre, Zambon Research, Cormano, Milano.
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000294:innervation*; D011954:Receptors, Dopamine / Q000502:physiology*
D011954:Receptors, Dopamine; D004298:Dopamine