Effects of atrial natriuretic peptide on systemic haemodynamics and cardiac function in normal man

Atrial natriuretic peptides (ANP) reduce blood pressure. Animal experiments suggest that this depressor action results from a reduction in cardiac output rather than peripheral vascular resistance but it is unresolved whether this is wholly due to their effect of reducing left ventricular filling or whether they have a negatively inotropic effect. We have therefore investigated the effects of ANP in normal man using Doppler measurements of ascending aortic blood flow. Six normal volunteers underwent infusions of placebo and incremental doses of ANP in the range 0.25 to 12 micrograms.min-1. Each infusion was given for 15 min and measurements made both in the supine and erect positions (passive tilt). In both positions ANP had dose dependent effects of increasing heart rate (HR) and maximal acceleration whilst lowering an index of systemic vascular resistance (ISVR). In the erect position ANP also lowered systolic blood pressure. In the 30 min after completion of the infusions there were significant decreases in peak velocity and cardiac output with increases in ISVR in both positions, but HR fell and diastolic pressure increased only when supine. During the course of the experiment mean haematocrit (SEM) increased from 43.9 (1.2) to 46.7 (1.0), indicating a mean reduction in plasma volume of 10.5%. This occurred despite a negative fluid balance of only 31(7) ml over the 2 h. These data suggest that ANP is not negatively inotropic and that, at pharmacological doses, it is an arteriolar dilator of rapid offset and reduces cardiac filling pressures by a mechanism of slower offset.