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beta-Human atrial natriuretic polypeptide (beta-hANP) is an antiparallel dimer of alpha-human ANP (alpha-hANP) that was isolated from human atria. Using synthetic beta-hANP and a radioimmunoassay for alpha-hANP that also detects beta-hANP, we have previously demonstrated that beta-hANP is converted into alpha-hANP in human plasma in vitro. In the present study, we compared the effects of intravenous administration of beta-hANP (100 micrograms) to five normal human volunteers with those of an equimolar administration of alpha-hANP (50 micrograms) to the same subjects, and we also investigated the possible mechanisms of actions of beta-hANP. Although the administration of alpha-hANP caused a significant decrease in blood pressure with a reactional increase of heart rate, beta-hANP elicited minimal change of blood pressure. In contrast, beta-hANP exerted more potent and longer lasting diuretic and natriuretic activities than did alpha-hANP. Net changes in urine volume and sodium excretion induced by beta-hANP (579 +/- 65 ml, 56.0 +/- 9.9 mEq) were significantly greater than those elicited by alpha-hANP (396 +/- 50 ml, 34.7 +/- 4.9 mEq; p less than 0.05, respectively). The administration of beta-hANP revealed a longer retention of the ANP-like immunoreactivity level in plasma, compared with that of alpha-hANP. High performance gel permeation chromatography coupled with the radioimmunoassay revealed that beta-hANP (Mr = 6000) was also converted into alpha-hANP (Mr = 3000) in human plasma in vivo. The demonstrated conversion of beta-hANP into alpha-hANP could be relevant to the observed effects of beta-hANP in humans.
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