Low-dose infusion of atrial natriuretic factor in mild essential hypertension

Intra-arterial blood pressure, cardiac output, heart rate, right heart indexes, urinary electrolytes, and urinary volume were monitored in eight patients with untreated (WHO Class I) essential hypertension. The patients were given synthetic atrial natriuretic factor (ANF) (99-126 α-hANP) at 1 and 2 pmol/kg/min in series (phases 1 and 2, 2 hours each dose) or vehicles (hemaccel) in random order on two separate occasions while on their usual diet. Arterial plasma ANF levels increased significantly from basal and time-matched placebo values from 25 ± 2 and 28 ± 3 pmol/l to 50 ± 4 and 83 ± 9 pmol/l at the end of phases 1 and 2, respectively (p <0.001). After 30 minutes during phase 2, systolic blood pressure decreased significantly by 20 ± 4 mm Hg (p <0.001) from basal and time-matched placebo values and remained significantly reduced (-17 ± 4 mm Hg, p <0.001) by the end of the recovery period (2 hours after infusions were completed). Pulmonary systolic blood pressure decreased by 5 ± 1 mm Hg (phase 2, p <0.05). Cardiac output decreased by 0.5 ± 0.1 l/min below baseline at the end of phase 2 of ANF infusion, whereas it increased significantly (p <0.02) by 0.6 ± 0.1 l/min during vehicle infusion. Systemic diastolic, pulmonary diastolic, righ atrial, and wedge pressures were not significantly changed during ANF or vehicle infusions, nor were pulmonary vascular resistance or heart rate altered. Systemic vascular resistance did not change significantly during both infusions, whereas during recovery, systemic vascular resistance decreased significantly after ANF infusion was discontinued (p <0.05). Microhematocrit levels increased dose dependently during ANF. The maximum increase was observed at the end of phase 2 (+4.7 ± 1.7%), whereas the microhematocrit level decreased to -2.4 ± 0.6% with vehicle (p <0.001) at the end of phase 2. Urinary sodium excretion increased significantly (p <0.02) by the end of phase 2 under ANF infusion (+38 ± 15%), whereas it decreased (-10 ± 6%) under placebo infusion by the end of phase 2. Urinary magnesium excretion was significantly increased during ANF infusion from phase 1 (p <0.02), whereas urinary potassium levels, calcium levels, creatinine levels, volume, and glomerular filtration rate did not differ significantly between the two infusions. Plasma renin, angiotensin II, aldosterone, and catecholamine concentrations did not change significantly during ANF or vehicle infusions. Our data suggest that increases in circulating arterial ANF levels to the upper limit of the ranges reported for humans with hypertension in absence of cardiac and renal failure reduce plasma volume and exert a selective lowering effect on systolic blood pressure without changing calculated peripheral vascular resistances.