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,
G. THIBAULT and
M. CANTIN
Clinical Research Institute of Montreal Montreal, Quebec, Canada H2W1R7
Address all correspondence and requests for reprints to: Dr. G. Thibault, Clinical Research Institute of Montreal, 110 Ouest avenue des Pins, Montreal, Quebec, Canada N2W 1R7.
A specific RIA was developed to measure plasma atrial natriuretic factor (ANF) N-terminal immunoreactivity in man. Antibodies raised in rabbits against a rat ANF N-terminal fragment [ANF-(11–37)] had 100% cross-reactivity with human ANF-(1–30) and purified plasma N-terminal ANF immunoreactivity. The ED80 and ED50 of standard curves prepared using [125I]human ANF-(l–30) and human ANF-(l–30) were 31.5 ± 5.4 (±SD) and 132.5 ± 20.4 fmol/tube, respectively. The plasma ANF N-terminal peptide concentrations were assayed directly, without extraction, since dilution of plasma and addition of standard to plasma yielded parallel dose-responses in the RIA and virtually 100% recovery of ANF-(1–30) added to plasma. Purification of ANF N-terminal immunoreactivity from 1.5 L human plasma by affinity chromatography and amino acid sequencing suggested that it was closely related to ANF-(l–98), although some degraded peptides were also detected.
The mean basal plasma ANF N-terminal peptide level measured in 34 normal subjects was 420 ± 157 (±SD) pmol/L. The values were higher in plasma from patients with congestive heart failure (grades III and IV; 7,041 ± 6,136 pmol/L; n = 13) or chronic renal failure (10,079 ± 4,942 pmol/L; n = 20). In 9 patients with chronic renal failure, hemodialysis resulted in a 30% (P < 0.05) decrease in plasma ANF-(99–126) levels, from 34.7 ± 12.3 (±SD) to 23.2 + 6.1 pmol/L, but no changes in plasma ANF N-terminal peptide concentrations.
These data indicate that the N-terminal portion of pro-ANF is cosecreted with ANF-(99–126). Its higher plasma levels in the basal state and during chronic renal failure suggest a different process of elimination than that of ANF-(99–126), which may be partly mediated by the kidney.
* This work was supported by a Group Grant from the Medical Research Council of Canada to the Multidisciplinary Research Group on Hypertension, the National Research Council, Bio-Méga, Inc., the Pfizer Co. (England), and the Canadian Heart Foundation.
Present address: University of Tromsö, Institute of Medical Biology, Tromsö, Norway.
Received July 29, 1987.
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