Lithium and the natriuretic response to gludopa, fenoldopam and dopamine [letter; comment]

Abstract

651Lithium and the natriuretic response to gludopa, fenoldopam and dopamine Girbes et al. (1990) recently reported that oral lithium (300 mg) had no effect on the renal response to DA1-dopamine receptor stimulation, by fenoldopam, in normal man. These results contrast with an earlier report by Jeffrey et al. (1988) that lithium (in a higher dose of 750 mg) abolished the natriuretic response to the renal dopamine prodrug gludopa, suggesting that lithium interacts with dopamine at the proximal tubule. Girbes et al. (1990) concluded that the interaction between lithium and the dopamine prodrug gludopa is not mediated by DA1-dopamine receptors or is confined to higher doses of lithium.These explanations both seem very unlikely in view of our results concerning the effect of lithium on the renal response to dopamine (Schoors & Dupont, 1990). Using a similar design and the same dose of lithium carbonate as Jeffrey, resulting in similar lithium levels, we did not find any effect of lithium pretreatment on the natriuretic response to dopamine infusion. This suggests that lithium does not interfere with the action of either dopamine or fenoldopam at the proximal tubule, and further suggests that the effect of lithium, observed on the action of gludopa, is not related to the dose of lithium. The fact that lithium does not reduce the natriuretic response to dopamine further indicates that the suggestion made by Girbes, that the lithium interaction may be mediated by DA2-dopamine or adrenergic receptors, is unlikely. Furthermore, to our knowledge the dopamine receptors, which have been demonstrated in the proximal tubule, using autoradiographic or radioligand binding studies, have been shown to belong to the DA1-subtype.Taken together, the present evidence suggests that lithium does not interfere with the action of dopamine or fenoldopam on the proximal tubular DA1-dopamine receptor. As lithium did markedly reduce the natriuretic response to gludopa, it is tempting to speculate that the proximal tubular response to intrarenally formed dopamine is different. Girbes etal. (1990) attributed the rise of plasma renin activity (PRA) by fenoldopam to direct DA1 stimulation, referring to Cavero et al. (1987). In fact Cavero etal. (1987) did demonstrate in in vivo experiments in rats that fenoldopam reduced blood pressure and that this blood pressure fall was accompanied by a reflex tachycardia and an increase in PRA. All of these responses were antagonized by pretreatment with a DA,-receptor antagonist. Therefore, in the in vivo situation, the increase in PRA after fenoldopam could, at least in part, be related to the fall in blood pressure, resulting in a baroreflex-mediated increase in sympathetic tone, and hence Padrenoceptor-mediated renin release. Girbes et al. (1990) did not provide any data on the blood pressure response to fenoldopam, but others have observed marked reductions in blood pressure in healthy volunteers, using similar doses (Allison et al., 1987). Using an infusion rate of fenoldopam of 0.05 ,ug kg-' min-1,...