It would seem established beyond peradventure that dopamine is formed in the kidney from circulating L-dopa. The likely site would appear to be the renal tubular cells but the contribution of the renal dopaminergic nerves needs further evaluation. Moreover it is probably that dopamine formed within the kidney acts there on specific receptors. This results in vasodilatation of renal blood vessels, by action on vascular receptors, and natriuresis, by an effect on tubular sodium transport mechanisms. Dopamine may form an integral part of the renal natriuretic cascade by, in its turn, evoking both the kallikrein-bradykinin system and the production of renal prostaglandins. Specific activation of the renal dopaminergic system by the administration of suitable agonists or renal prodrugs may prove possible in the future. Abnormalities in the renal production of dopamine may be important in several hypertensive and oedematous disorders. Further work will be required to establish a possible role for dopamine in these conditions and to determine whether they will benefit from treatment with suitable dopamine agonists. Dopamine, once regarded as of little importance outside the central nervous system, has certainly come to occupy a central place in renal salt handling. The ratio of dopamine production in the kidney to that for renin may be of pivotal importance in the control of systemic arterial pressure.

1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion.

gamma-L-Glutamyl-L-dopa was given by intravenous infusion to eight normal subjects at doses of 12.5 and 100 micrograms min-1 kg-1. Both doses of the dipeptide resulted in an increase in mean urinary sodium excretion. Mean effective renal plasma flow rose at both doses, but mean glomerular filtration rate increased only at the lower dose. There was a fall in mean plasma renin activity after the infusion of both 12.5 and 100 micrograms min-1 kg-1. Mean urine free dopamine excretion increased by 280- and 2500-fold at infusion rates of 12.5 and 100 micrograms min-1 kg-1 respectively. Mean plasma free dopamine rose at both doses but the increase at 12.5 micrograms min-1 kg-1 was not to a level previously associated with systemic effects of the catecholamine. On administration of the dipeptide at 12.5 micrograms min-1 kg-1 there were no changes in blood pressure or heart rate, but at the higher dose there was a fall in diastolic blood pressure. At a dose of 12.5 micrograms min-1 kg-1 in man, there is kidney specific conversion of gludopa to dopamine.

1. Plasma and urine free dopamine were measured daily for 5 days in six normal subjects maintained on a low sodium diet. The subjects were then given dietary supplements of sodium chloride for 5 days and the measurements repeated. 2. Throughout the experiment the 24 h free dopamine excretion rates for all the subjects were higher than could be accounted for by renal clearance. Dopamine excretion increased significantly in response to the added sodium chloride whereas plasma dopamine remained unchanged. The rise in dopamine excretion preceded that of sodium excretion. 3. It is concluded that free dopamine is formed within the kidney in response to increased dietary sodium and may have a role in the control of sodium excretion.