Renal dopaminergic mechanisms in renal parenchymal diseases and hypertension

The present report addresses the status of the renal dopaminergic system ac tivity in patients afflicted with different renal disorders and in the remn ant kidney of uninephrectomized (UNX) rats, based on the urinary excretion of L-DOPA, dopamine and amine metabolites. In renal transplant recipients w ith good recovery of graft function (group 1, n = 11), the daily urinary ex cretion of DOPAC, but not that of HVA, was found to increase progressively throughout the first 12 days post-transplantation from 698 +/- 57 nmol in t he first day to 3498 +/- 414 nmol on day 9, and then remained constant unti l day 12. This resulted in a 6-fold increase in the urinary DOPAC/dopamine ratios. In renal transplant recipients with acute tubular necrosis (group 2 , n = 8), the urinary levels of dopamine, DOPAC and HVA were similar to 30% of those in group 1. Tn a group of 28 patients with chronic renal parenchy mal disorders, the daily urinary excretion of L-DOPA, free dopamine and dop amine metabolites (DOPAC and HVA) correlated positively with the degree of deterioration of renal function (P<0.01). However, the UDopamine/L-DOPA and U-DOPAC/Dopamine ratios in patients with chronic renal insufficiency were found to be similar to those observed in patients with normal renal functio n. In 14 IgA nephropathy (IgA-N) patients with near normal renal function, the changes in 24 h mean blood pressure when going from 20 to 350 mmol/day sodium intake correlated negatively with the daily urinary excretion of dop amine (r(2)=0.597, P<0.01). The urinary excretion of L-DOPA and dopamine in IgA-N patients with salt-sensitive (SS) blood pressure was lower than in s alt-resistant (SR) patients (P<0.05), irrespective of their daily sodium in take. However, the rise in urinary dopamine output during salt loading (fro m 20 to 350 mmol/day) was greater (P<0.05) in IgA-N SS patients (21.2+/-2.5 % increase) than in SR patients (6.3+/-1.4% increase). Fifteen days after t he surgery, uninephrectomy (UNX) in the rat was accompanied by an enhanced (P<0.05) urinary excretion of dopamine (36+/-3 vs 26+/-2), DOPAC (124+/-11 vs 69+/-6) and HVA (611+/-42 vs 354+/-7) (nmol/g kidney/kg body weight). Th is was accompanied by an increase in V-max values for renal aromatic L-amin o acid decarboxylase in the remnant kidney of UNX rats (P<0.05). Sch 23390, a D-1 dopamine receptor antagonist, produced a marked reduction in the uri nary excretion of sodium in UNX rats, whereas in sham-operated rats the dec rease in urinary sodium did not attain a significant difference. It is conc luded that the study of the renal dopaminergic system in patients afflicted with renal parenchymal disorders should address parameters other than free urinary dopamine, namely the urinay excretion of L-DOPA and dopamine metab olites (DOPAC and HVA). It is also suggested that in SS hypertension of chr onic renal parenchymal diseases, renal dopamine produced in the residual tu bular units may be enhanced during a sodium challenge, thus behaving approp riately as a compensatory natriuretic hormone.