Arteriovenous ratios of angiotensin II during acute infusion experiments: a model-based analysis

The hormone angiotensin II (AII) is a vasoconstrictor known to participate in the natural regulation of blood pressure via the renin-angiotensin system. A third-order model was developed which describes the dynamics of venous and arterial plasma AII concentrations (PAC) and mean arterial blood pressure (BP) during acute constant rate AII infusion experiments. The model is calibrated using approximate blood circulation rates and steady-state PAC and BP data for published experiments in sheep. Analysis of the dynamic model demonstrates that local changes in PAC during the first several minutes of acute infusion are characterized by the comparatively rapid distribution of exogenous AII making its forward passage across the blood circulation, combined with the more gradual elevation of exogenous AII recycled through the circulation. This analysis explains the observed divergence in physiological levels of venous and arterial PAC at steady state in terms of the monotonic net clearance of elevated levels of circulating AII along the circulatory path between the point of infusion and the two sites at which the PAC measurements are taken. The model suggests that the differing arteriovenous AII concentration ratios and differing PAC and BP relationships reported for different dose-response experiments may be explained in part by differences in the specific infusion and measurement sites employed in those experiments.