Blood clearance rates of angiotensin II and its metabolites in sheep: presence of immunoreactive fragments in arterial blood.

1. The blood clearance rates of exogenous (des-1-Asp)-angiotensin II and (des-1-Asp-2-Arg)-angiotensin II calculated from the arterial blood level during steady state infusion in conscious sodium-replete sheep were found to be 125 litre/h (s.d. = 27, n = 18) and 188 litre/h (s.d. = 23, n = 18), respectively. These blood clearance rates were in the same order as values for angiotensin II previously reported. 2. Using descending paper chromatography, immunoreactive fragments of angiotensin II in arterial blood extracts were adequately separated from angiotensin II. Quantitative determination of angiotensin II by direct immunoassay on whole blood extract using recovery tracer to correct for losses during extraction were on the average 31% (n = 9) higher than those obtained after the same blood extract had been subjected to chromatographic separation. 3. The blood clearance rates of exogenous 1-Asp-5-Ile-angiotensin II calculated from infusion rate/blood angiotensin II concentration before and after chromatographic separation were significantly different, being 103 litre/h (s.d. = 16, n = 18) and 134 litre/h (s.d. = 25, n = 9), respectively (P less than 0.001;t-test, 16 d.f.). 4. Our data demonstrate the presence of immunoreactive fragments of angiotensin II in arterial blood of sheep during steady-state infusion and indicate that direct immunoassay on arterial blood extracts without adequate separation may result in artificially higher values of angiotensin II in blood and consequently false value for its clearance rate.