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, alpha-human
ANP (
alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with
essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without
metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of
alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with
essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with
essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of
alpha-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
alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of
alpha-hANP increased plasma
cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with
essential hypertension. The rise in plasma
cyclic GMP by
alpha-hANP was suppressed by MC both in normal subjects and patients with
essential hypertension. Urinary
cyclic GMP excretion also increased during the infusion of
alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma
aldosterone concentration (PAC), which was depressed by
alpha-hANP in normal subjects and patients with
essential hypertension, was increased by MC. These results suggest that the hypotensive effect of
alpha-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.