WE have previously suggested that immunologically reactive fragments of angiotensin II may arise in blood during the metabolism of the octapeptide by angiotensinases and that such an occurrence could compromise the measurement of blood angiotensin II by radioimmunoassay1. This proposal regarding the presence of angiotensin II fragments in blood has now been investigated by paper chromatography of ethanolic blood extracts and radio-immunoassay of eluates from serial sections along the chromatograms to detect immunoreactive angiotensin II fragments. The octapeptide angiotensin II was the predominant peptide detected in arterial blood samples from six human subjects and nine sheep, being 85 and 96 per cent of the total immunoreactivity respectively. In contrast to this finding in arterial blood, angiotensin II was a minor component in the chromatographic pattern of extracts of venous blood from six human subjects, comprising only 28 per cent of the total immunoreactivity. The major immunoreactive component present in venous blood possessed the mobility of the (3–8) hexapeptide of angiotensin II. These results indicate that radioimmunoassay of angiotensin II in ethanolic arterial blood extracts gives values which are close to the amount of the octapeptide actually present. The same radioimmunossay may, however, substantially over-estimate the true level of the octapeptide present in venous blood because of interference by the immunoreactive metabolites of angiotensin. The arterio-venous difference of the chromatographically isolated angiotensin II measured by the radioimmunoassay is consistent with bioassay observations that approximately two-thirds of the circulating angiotensin II is extracted and metabolized across tissue vascular beds. Measurement of the total immunoreactive angiotensin content of venous blood by radioimmunoassay of angiotensin II shows moderately good correlation with the arterial level of the octapeptide, and is probably adequate for clinical studies. Radioimmunoassay of blood angiotensin II during physiological studies on the role of angiotensin II in vascular and hormonal regulation should, however, be performed on arterial blood samples in order to obtain a true estimate of the concentration at which the octapeptide is presented to its target tissues.
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Catt, K. J., Cain, M. D., and Coghlan, J. P., Lancet, ii, 1005 (1967).
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CAIN, M., CATT, K. & COGHLAN, J. Immunoreactive Fragments of Angiotensin II in Blood. Nature 223, 617–618 (1969). https://doi.org/10.1038/223617a0
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