Vol. 148, No. 3, 1987 November 13, 1987 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 1540-1548 ATRIAL NATRIURETIC PROHORMONE PEPTIDES 1-30, 31-67, and 79-98 VASODILATE THE AORTA David L. Vesely 1, James S. Norris1, 2, J. Michael Walters 3, Robert R. Jespersen 3, and Dennis A. Baeyens 3 Departments of Medicine I and Physiology2, University of Arkansas for Medical Sciences, John L. McClellan Memorial Veterans Hospital, and Department of Biology3, University of Arkansas at Little Rock, Little Rock, Arkansas 72205 Received October 9, 1987 SUMMARY: Humanprohormone atrial natriuretic peptides 1-30, ?~-l-L-~'f~--, and 79-98 caused vasodilation of porcine aortas which began in 30 seconds and was maximal at 10 minutes. These three peptides were found to be equally potent to atrial natriuretic factor in their vasodilatory activity which was found with or without endothelium present. This vasodilation was associated with a 4 to 5 fold increase in cyclic GMP in the aorta secondary to activation of particulate guanylate cyclase [E.C. 4.6.12]. These data demonstrate that three N-terminal peptide segments of the atrial natriuretic factor prohormone cause vasodilation. © 1987 Academic Press, Inc. Atrial natriuretic factor (ANF) is formed by proteolytic separation of the final 28 amino acids at the carboxy terminal end of its 126 amino acid prohormone (Fig. 1). Both trypsin and thrombin can break the arginine-serine bond between amino acids 98-99 to form ANF (1). Both trypsin and thrombin may also break a similar bond between amino acids 67-68 (arginine-aspartic acid) to form peptide fragment 1-67. In addition to trypsin and thrombin there is a large family of asparatic proteases [E.C. 4.23] in the circulation (2-6). Three peptides that one might expect to be formed by asparatic proteases attacking the asparatic acid bonds in this prohormone would consist of amino acids 1-30, 31-67 and 79-98 (Fig. 1). We have recently discovered in studying 54 normal humans that two of these peptides consisting of amino acids 1-30 (i.e. pro ANF 1-30) and amino acids 31-67 (i.e. pro ANF 31-67) circulate in man (7). (We 0006-291X/87 $1.50 Copyright © 1987 by Academic Press, Inc. All rights of reproduction in any form reserved. 1540