Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure - RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (±SE) increased from net reabsorption during control of 111 ± 27 ml/h to net filtration of 1,219 ± 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued. Because ANP was not significantly increased until 30 min postinfusion, it appears that factors other than ANP, such as increased vascular pressures, baroreceptor-mediated vasodilation, and hemodilution of plasma proteins, initiate responses to intravascular fluid loading. ANP may, in part, mediate the renal response to saline infusion.