The renal effects of dopamine, the dopamine antagonist spiperone and the combination of dopamine and spiperone were examined in the isolated perfused rat kidney preparation. Studies were carried out at constant perfusion pressure and the following were measured at 10 min intervals for 1 h: perfusate flow; GFR (3H-inulin); urine flow rate; sodium, potassium and kallikrein excretion; perfusate renin concentration; perfusate and urinary-dopamine levels. Low-dose dopamine infusion (6 X 10(-10) mol/min) resulted in significant diuresis, natriuresis and kaluresis but little change in GFR. These effects were blocked by spiperone (10(-10) mol/min) which had no significant effects when infused alone. At a higher dose (10(-8) mol/min) dopamine significantly increased urine flow alone; this too was reversed by spiperone. Dopamine had no significant effects on perfusate flow, renin release or kallikrein excretion. Perfused control kidneys excreted amounts of dopamine (328 pmol/h, s.e.m. = 57, n = 6) far in excess of kidney dopamine content (49 pmol/g, s.e.m. = 6, n = 32). Renal handling of infused dopamine was dose-related; the fraction of the administered dose taken up and/or metabolized by the kidney on the higher dose infusion was considerably less than on the lower dose (40%, s.e.m. = 3 vs. 82%, s.e.m. = 6) while more was excreted (13%, s.e.m. = 3 vs. 2%, s.e.m. = 1). These studies indicate that dopamine at low doses can produce diuresis, natriuresis and kaluresis independently of extrarenal or haemodynamic influences and not mediated by renal renin or kallikrein systems. The kidney also exhibits a saturable capacity for dopamine uptake and/or metabolism.

In the rat kidney catecholaminergic nerve elements were identified by fluorescence histochemistry in perivascular plexuses around corticula arteries and juxtaglomerular arterioles and in medullary vascular bundles. Fluorescence was abolished in all areas 24 h after treatment with 6-hydroxydopamine (6-OHDA; 150 mg/kg i.v.). Protection of noradrenergic endings from destruction by 6-OHDA was afforded by pretreatment with desipramine (DMI; 25 mg/kg i.p.) which restored fluorescence towards control levels. By semiquantitative analysis fluorescence was identical in juxtaglomerular regions but slightly reduced around larger vessels in (DMI + 6-OHDA)-treated rats when compared to controls. Changes in tissue noradrenaline content, but not dopamine content, paralleled the changes in nerve fluorescence. Noradrenaline content was 4.10 pmol/mg protein (s.e.m. = 0.22, n = 32) in controls and was reduced by 90% to 0.40 pmol/mg (s.e.m. = 0.05, n = 23) in 6-OHDA-treated and by 26% to 3.01 pmol/mg (s.e.m. = 0.21, n = 23) in (DMI + 6-OHDA)-treated rats. Kidney dopamine content was 0.38 pmol/mg protein (s.e.m. = 0.05, n = 32) in controls and was reduced by 55% to 0.18 pmol/mg (s.e.m. = 0.02, n = 17) in 6-OHDA-treated and by 53% to 0.17 pmol/mg (s.e.m. = 0.02, n = 23) in (DMI + 6-OHDA)-treated rats. The renin response to haemorrhage was examined in pentobarbitone sodium-anaesthetized rats as a test of functional integrity of renal nerves in the three groups. Progressive 1 ml haemorrhages (to total blood loss of 4 ml, 1.3% body weight) resulted in similar increases in plasma renin activity in controls and (DMI + 6-OHDA)-treated animals but the response was significantly attenuated in 6-OHDA-treated rats. Renal catecholaminergic nerves appear to be predominantly noradrenergic. It is doubtful if a significant intrarenal dopaminergic system exists in the rat.