Domperidone, a DA2-specific dopamine antagonist, has no effect on the renal or haemodynamic response to atrial natriuretic peptide in man.
1. Animal experiments have suggested that the renal effects of atrial natriuretic peptide (ANP) are dependent on dopaminergic activation, predominantly of the DA1-receptor. In man, there is evidence of dependence on the DA2-receptor for the natriuresis produced by central blood volume expansion. 2. Six normal volunteers underwent infusions of alpha-human ANP preceded by domperidone (a DA2-antagonist) or placebo. Eight volunteers underwent a 3 h period of 10 degrees head-down tilt also preceded by domperidone or placebo. 3. Both the ANP infusion and head-down tilt produced a significant diuresis and natriuresis, neither of which was antagonized by the presence of domperidone. 4. The ANP infusion significantly reduced diastolic blood pressure and produced significant increases in the Doppler-measured aortic blood velocity variables of peak velocity and maximal acceleration. Domperidone had an independent effect of increasing blood pressure but did not appear to have a specific interaction with the haemodynamic effects of ANP. 5. Head-down tilt reduced mean arterial pressure and heart rate and increased maximal acceleration. Again, an independent effect of domperidone was seen on blood pressure. Heart rate and maximal acceleration showed similar changes in the presence of domperidone. 6. Domperidone does not antagonize the renal or haemodynamic effects of ANP and if dopaminergic activation is necessary for the renal action of ANP it is unlikely to be mediated by the DA2-receptor.
Allen
M J
MJ
Department of Medicine One, St George's Hospital Medical School, London.
Ang
V T
VT
Bennett
E D
ED
D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D011187:Posture; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D004294:Domperidone; D009320:Atrial Natriuretic Factor