The renal dopaminergic system, neurohumoral activation, and sodium handling in heart failure

Dopamine of renal origin exerts natriuretic and diuretic actions by activating specific receptors located in the renal proximal tubular epithelial cells. Heart failure (HF) is accompanied by activation of several neurohumoral systems. The interaction of these systems with the renal dopaminergic system and its effect on sodium handling in HF are not clarified.

We studied 13 patients with decompensated New York Heart Association class III/IV HF and 17 sex- and age-matched patients with mild to moderate stable class I/II HF. We measured plasma catecholamines, aldosterone, type B natriuretic peptide (BNP), sodium, creatinine (UCr), and 24-hour urinary excretion of sodium, UCr, levo-3,4-dihydroxyphenylalanine (L-DOPA), 3-o -methyldopa, dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovallinic acid, and norepinephrine. All patients had HF of ischemic etiology. No statistically significant differences were found between the groups with respect to urine volume (1.79 +/- 0.23 L x d(-1) vs 2.20 +/- 0.18 L x d(-1), P =.18) and urinary sodium (161.3 +/- 27.5 mmol x d(-1) vs 232.9 +/- 28.8 mmol x d(-1), P =.12). Urinary L-DOPA was significantly lower in patients with decompensated class III/IV HF than in the other group (79.0 +/- 13.8 nmol x g UCr(-1) vs 108.4 +/- 10.3 nmol x g UCr(-1), P =.04). Urinary dopamine showed a nonstatistically significant trend to be slightly higher (1294.3 +/- 188.5 nmol x g UCr(-1) vs 953.2 +/- 107.4 nmol x g UCr(-1), P =.14). Consequently, urinary dopamine/L-DOPA ratios were markedly higher in patients with decompensated class III/IV HF than in the other patients (20.6 +/- 3.4 vs 9.0 +/- 0.9, P <.001). Plasma L-DOPA (38.1 +/- 4.4 pmol x mL(-1) vs 40.0 +/- 3.0 pmol x mL(-1), P =.48), dopamine (37.0 +/- 6.3 pmol x mL(-1) vs 41.1 +/- 2.6 pmol x mL(-1), P =.53), 3,4-dihydroxyphenylacetic acid (51.7 +/- 11.7 pmol x mL(-1) vs 56.5 +/- 5.4 pmol x mL(-1), P =.09), and norepinephrine (9.5 +/- 2.4 pmol x mL(-1) vs 5.6 +/- 1.0 pmol x mL(-1), P =.12) did not differ between groups. Plasma aldosterone (180.2 +/- 28.0 pg x mL(-1) vs 69.9 +/- 13.3 pg x mL(-1), P <.001) and BNP (677.5 +/- 133.9 pg x mL(-1) vs 389.4 +/- 88.4 pg x mL(-1), P <.04) levels were higher in the decompensated class III/IV HF group than in the other group, whereas serum sodium was lower (137.3 +/- 1.2 mmol x L(-1) vs 143.2 +/- 1.0 mmol x L(-1), P =.001).

These results suggest that, in patients with HF, the increased renal utilization of L-DOPA may constitute a compensatory mechanism, activated in response to stimuli leading to sodium reabsorption.