The dopamine receptor antagonist haloperidol blocks natriuretic but not hypotensive effects of the atrial natriuretic factor

The dopamine receptor antagonist haloperidol blocks natriuretic but not hypotensive effects of the atrial natriuretic factor. Acta Physiol Scand 130 , 401–407. Received 11 December 1986, accepted 10 February 1987. ISSN 0001–6772. Department of Physiology & Medical Biophysics and Department of Pharmacology, Biomedical Centre, University of Uppsala, Sweden. Studies were performed on anaesthetized male Münich‐Wistar rats to investigate the influence of the dopamine (DA) receptor antagonist haloperidol on the natriuretic response to infusion of a synthetic atrial natriuretic factor. The whole kidney glomerular filtration rate (GFR), urinary excretion of electrolytes, and arterial blood pressure (BP) were therefore measured in groups of animals pretreated with haloperidol or vehicle and given a continuous intravenous infusion of atrial natriuretic peptide (ANP; 28 amino acids). Forty‐five minutes of ANP infusion at 10 μg h ‐1 kg ‐1 body wt did not increase GFR (change from 1.14 ± 0.08 to 1.15 ± 0.05 ml min ‐1 g ‐1 kidney wt). Sodium excretion ( U Na V ) increased more than four‐fold from 0.037 ± 0.008 to 0.165 ± 0.070 μmol min ‐1 g ‐1 kidney wt ( P 0.01). Potassium excretion ( U K V ) increased by 86% ( P 0.001) and the urine flow rate ( V ) increased transiently by 63% ( P 0.05) and did not differ from the control value during the last 15 min of ANP infusion. The urinary sodium concentration ( U Na ) increased almost three‐fold, while BP decreased by 14%. There was no change in urine osmolality. In animals pretreated with haloperidol (I mg kg ‐1 body wt), 45 min of ANP infusion did not significantly alter GFR (from 1.10 ± 0.08 to 0.98 ± o.09 ml min ‐l g ‐1 kidney wt). The U Na V did not increase significantly (change from 0.026 ± 0.006 to 0.030 ± 0.009 μ mol min ‐1 g ‐l kidney wt). The U K V was not elevated by ANF infusion. The urine flow rate was transiently elevated by 45% but was not different from the control during the last 15 min of infusion. Both U Na and U osm remained unchanged, but BP was reduced by 11%. In conclusion, the DA receptor blocking agent haloperidol blunts the natriuretic effect of ANP. This action is probably exerted by inhibiting the postulated tubular effects of ANP through an unknown mechanism, but not the vascular ones, since the hypotensive effect of ANP is unaltered. Atrial natriuretic peptide increases sodium excretion not, mainly, by increasing GFR but by affecting tubular transport processes.