Dose-response study of the redistribution of intravascular volume by angiotensin II in man

Abstract

1. The response of systemic and regional haemodynamic indices to increasing infusion rates of angiotensin II (1, 3 or 10 ng min−1 kg−1) or placebo [5% (w/v) d-glucose] was studied in eight normal male subjects. 2. As compared with placebo, angiotensin II infusion caused an incremental rise in the serum angiotensin II level [14.5 ± 7.7 (placebo) to 187.2 ± 36.1 (10 ng of angiotensin II min−1 kg−1) pmol/l; mean ± 95% confidence interval] associated with a stepwise increase in total peripheral resistance [880 ± 42 (placebo) to 1284 ± 58 (10 ng of angiotensin II min−1 kg−1) dyn s cm−5] and a progressive reduction in cardiac output [8.3 ± 0.4 (placebo) to 7.0 ± 0.4 (10 ng of angiotensin II min−1 kg−1) litres/min]. 3. A stepwise fall in renal blood flow was observed with increasing angiotensin II infusion rate [1302 ± 65 (placebo) to 913 ± 64 (10 ng of angiotensin II min−1 kg−1) ml/min]. In contrast, calf blood flow was unaffected by 1 ng or 3 ng of angiotensin II min−1 kg−1 and was significantly increased by 10 ng of angiotensin II min−1 kg−1 (P < 0.01). 4. Calf venous capacitance was uninfluenced by 1 ng of angiotensin II min−1 kg−1, but was significantly increased by both 3 ng (P < 0.005) and 10 ng (P < 0.001) of angiotensin II min−1 kg−1. 5. Our results indicate that the pressor response to angiotensin II is a summation of multiple regional haemodynamic effects which differ qualitatively not only with the vascular bed studied but also within a single tissue, with the level of circulating angiotensin II attained. 6. The venodilatation we have demonstrated with high angiotensin II levels may effect a potentially favourable redistribution of blood flow in situations of inappropriate extracellular fluid volume expansion, such as chronic heart failure.