ANP-mediated volume depletion attenuates renal responses in humans

Brief low-dose infusions of atrial natriuretic peptide (ANP) that emulate physiological plasma concentrations in humans have little if any effect on renal excretory function. This study explored the possibility that ANP-mediated reductions in cardiac filling pressures (through ANP's rapid effect on capillary dynamics) could attenuate its purported renal effects. Protocol A consisted of 16 healthy subjects (ages 19-27 yr old) who underwent three consecutive 45-min experimental sequences: 1) placebo, 2) ANP (10 ng.kg-1 x min-1), and 3) ANP alone (n = 8) or ANP with simultaneous lower body positive pressure (LBPP, n = 8). Electrocardiogram and direct measures of arterial and central venous pressures were continuously monitored. Blood was sampled at the end of each 45-min sequence before subjects stood to void. Compared with control (placebo), ANP produced a hemoconcentration and increased plasma norepinephrine, but did not change heart rate, blood pressure, plasma levels of renin, aldosterone, or vasopressin, or renal excretion of volume or sodium. In subjects receiving LBPP to maintain central venous pressure during the last 45 min of ANP infusion, norepinephrine did not increase and urine volume and sodium excretion increased (P < 0.05). In a second study (protocol B), five healthy subjects received a placebo infusion for 45 min followed by two consecutive 45-min infusions of ANP (10 ng.kg-1 x min-1). Central venous pressure was maintained (LBPP) at placebo baseline throughout the two ANP infusion periods. Urine volume and sodium excretion rates increased progressively and significantly during both ANP infusion periods (P < 0.05) without significant changes in creatinine clearance, blood pressure, or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)