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Human atrial natriuretic factor (h-ANF) or its vehicle only, were infused at rates of 0.8, 1.6 and 3.2 μg/min over three successive 30-min periods, into five patients with mild essential hypertension and seven normotensive controls. Baseline (mean ± s.e.m.) plasma ANF levels were 13 ± 2 in patients and 8 ± 1 pg/ml in controls. During the first period, plasma ANF and cyclic guanosine monophosphate (cGMP) levels increased in both groups without significant alteration of blood pressure, heart rate, diuresis, natriuresis or cGMP excretion rate. During the second period of infusion, plasma ANF levels increased up to 179 ± 39 and 177 ± 30 pg/ml in patients and controls and plasma cGMP concentrations increased x 5.0 and x 4.9, respectively; natriuresis increased x 2.4 in patients and x 3.1 in controls while urinary cGMP increased x 10.9 in patients and x 10.5 in controls. During the last period, three controls became hypotensive while blood pressure remained stable in the other controls and in the patients with essential hypertension. During this period, the increases in plasma ANF concentration, diuresis, natriuresis and urinary cGMP excretion were similar in both groups. However, the mean plasma cGMP concentration after 90 min infusion was significantly higher in hypertensive patients than in control subjects (30.7 ± 3.3 versus 15.6 ± 3.4 pmol/ml, P < 0.05). The haif-life and clearance of plasma ANF, upon discontinuation of the infusion, were similar in both groups.Our data suggest that patients with mild essential hypertension have enhanced increases in plasma cGMP but normal increases in diuresis, natriuresis and cGMP excretion following infusion of h-ANF at pharmacological rates.