This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide (ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, α-human ANP (α-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01μg/kg/min for 30 minutes, and then 0.03μg/kg/min with or without metoclopramide (MC) for 30 minutes. After the infusion of the 0.03μg/kg/min dose of α-hANP, systolic blood pressure fell from 115±17mmHg to 109±15mmHg in normal subjects, and fell significantly from 163±33mmHg to 145±26mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101±14mmHg to 92±7mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03μg/kg/min of α-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of α-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03μg/kg/min dose of α-hANP increased plasma cyclic GMP concentration from 4.1±2.1pmol/ml to 34.3±25.0pmol/ml in normal subjects and from 4.5±2.6pmol/ml to 20.3±7.4pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by α-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of α-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by α-hANP in normal subjects and patients with essential hypertension, was increased by MC.
These results suggest that the hypotensive effect of α-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.
