Renal dopaminergic mechanisms in renal parenchymal diseases and hypertension.
The present report addresses the status of the renal dopaminergic system activity in patients afflicted with different renal disorders and in the remnant kidney of uninephrectomized (UNX) rats, based on the urinary excretion of L-DOPA, dopamine and amine metabolites. In renal transplant recipients with good recovery of graft function (group 1, n=11), the daily urinary excretion of DOPAC, but not that of HVA, was found to increase progressively throughout the first 12 days post-transplantation from 698+/-57 nmol in the first day to 3498+/-414 nmol on day 9, and then remained constant until 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 approximately 30% of those in group 1. In a group of 28 patients with chronic renal parenchymal disorders, the daily urinary excretion of L-DOPA, free dopamine and dopamine metabolites (DOPAC and HVA) correlated positively with the degree of deterioration of renal function (P<0.01). However, the U(Dopamine/(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 function. 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 dopamine (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 salt-resistant (SR) patients (P<0.05), irrespective of their daily sodium intake. However, the rise in urinary dopamine output during salt loading (from 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 the 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). This was accompanied by an increase in V(max) values for renal aromatic L-amino acid decarboxylase in the remnant kidney of UNX rats (P<0.05). Sch 23390, a D1 dopamine receptor antagonist, produced a marked reduction in the urinary excretion of sodium in UNX rats, whereas in sham-operated rats the decrease in urinary sodium did not attain a significant difference. It is concluded 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 urinary excretion of L-DOPA and dopamine metabolites (DOPAC and HVA). It is also suggested that in SS hypertension of chronic renal parenchymal diseases, renal dopamine produced in the residual tubular units may be enhanced during a sodium challenge, thus behaving appropriately as a compensatory natriuretic hormone.
Pestana
M
M
Departments of Nephrology, and Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal.
Jardim
H
H
Correia
F
F
Vieira-Coelho
M A
MA
Soares-da-Silva
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology / Q000503:physiopathology; D008954:Models, Biological; D051381:Rats; D019459:Urothelium / Q000502:physiology / Q000503:physiopathology
D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid