Evidence for an involvement of dopamine receptors in the natriuretic response to atrial natriuretic peptide.
Intravenous injection of atrial natriuretic peptides (ANP) induces a preferential vasodilatation of the renal resistance vessels. A similar effect is exerted by dopamine. Exogenous administration of this catecholamine induces, like the atrial peptides, diuresis and natriuresis, an effect prevented by dopamine receptor antagonists. In view of these parallels, the influence of dopamine antagonists on the diuretic response of anaesthetized rats to ANP was tested. The unselective dopamine antagonists haloperidol (50 micrograms, i.v.) and chlorpromazine (50 micrograms, i.v.) prevented the diuretic and natriuretic effect of a partially purified atrial extract, and significantly blunted that of alpha-hANP (1 microgram). Dopamine receptors are classified as DA-1 and DA-2. The DA-2 receptor antagonists metoclopramide (50 micrograms, i.v.) and sulpiride (50 micrograms, i.v.) did not affect ANP induced natriuresis. The DA-1 receptor antagonists SCH 23390 and SK&F 83566 dose-dependently counteracted the renal response to the intravenous administration of ANP. The administration of haloperidol (25, 50 and 100 micrograms, i.v.) to rats undergoing a putative ANP dependent natriuresis (isotonic saline loading) dose-dependently reduced both urine volume and sodium excretion. Atriopeptin II (10(-9)-10(-10) M) displaced tritiated spiperone, a dopamine antagonist, from specific binding sites in homogenates of renal medulla, papilla and cortex. These results suggest that dopamine receptors, most probably of the DA-1 subclass, are involved in the natriuretic response to ANP. The present experiments do not allow the conclusion as to whether ANP directly interacts with the dopamine receptors or whether it affects these receptors by releasing dopamine.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D018492:Dopamine Antagonists; D007668:Kidney / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D012965:Sodium Chloride; D013134:Spiperone; D009320:Atrial Natriuretic Factor