Low-Dose Infusion ofAtrial Natriuretic Factor inMildEssential Hypertension

Intra-arterial blood pressure,cardiac output, heart rate, right heart indexes, urinary electrolytes, andurinary volumewere monitored ineight patients withuntreated (WHO Class I)essential hypertension. Thepatients weregivensynthetic atrial natriuretic factor (ANF)(99-126 a -hANP) at 1and2pmol/kg/min inseries(phases 1and2,2hours eachdose) orvehicle (hemaccel) inrandom order on twoseparate occasions while on their usual diet. Arterial plasma ANF levels increased significantly frombasal andtime-matched placebo values from25±2and28+3pmol/1to50±4and 83±9pmol/l attheendofphases 1and2,respectively (p<0.001). After 30minutes during phase 2,systolic blood pressuredecreased significantly by20±4mm Hg (p<0.001) frombasaland time-matched placebo values andremained significantly reduced (-17±4 mm Hg,p<0.001) bythe endoftherecoveryperiod (2hoursafter infusions were completed). Pulmonary systolic blood pressuredecreased by5±1mm Hg(phase 2,p<0.05). Cardiac output decreased by0.5±0.11/min belowbaseline attheendofphase 2ofANFinfusion, whereas itincreased significantly (p<0.02) by 0.6±0.1 1/min during vehicle infusion. Systemic diastolic, pulmonary diastolic, right atrial, and wedgepressureswere notsignificantly changed during ANF or vehicle infusions, nor were pulmonaryvascular resistance orheart ratealtered. Systemic vascular resistance didnotchange significantly during bothinfusions, whereas during recovery,systemic vascular resistance decreased significantly after ANFinfusion was discontinued (p<0.05). Microhematocrit levels increased dose dependently during ANF.Themaximumincrease wasobserved attheendofphase 2(+4.7±1.7%), whereas themicrohematocrit level decreased to-2.4±0.6%withvehicle (p<0.001) attheendof phase2.Urinary sodiumexcretion increased significantly (p<0.02) bytheendofphase2under ANFinfusion (+38±15%), whereas itdecreased (-10±6%)underplacebo infusion bytheendof phase 2.Urinary magnesium excretion was significantly increased during ANFinfusion fromphase 1 (p<0.02), whereasurinary potassium levels, calcium levels, creatinine levels, volume, and glomerular filtration ratedidnotdifersignificantly between thetwoinfusions. Plasmarenin, angiotensin H, aldosterone, andcatecholamine concentrations didnotchange significantly during ANF orvehicle infusions. Ourdatasuggest thatincreases incirculating arterial ANFlevels tothe upperlimit oftherangesreported forhumanswithhypertension inabsence ofcardiac orrenal failure reduce plasma volumeandexert aselective lowering effect onsystolic bloodpressure without changing calculated peripheral vascular resistances. (Circulation 1989;80:893-902)