Journal of Clinical Endocrinology & Metabolism, Vol 71, 1138-1146, Copyright © 1990 by Endocrine Society

ARTICLES

Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas

DL Vesely, WC Arnold, CJ Winters, AL Sallman and DM Rico
Department of Medicine, University of South Florida for Health Sciences, Tampa 33612.

To investigate the possible relationship of hypertension and the N- terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF- (31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and - (31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C- terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas.

This article has been cited by other articles:

				D. L Vesely Atrial natriuretic peptides in pathophysiological diseases Cardiovasc Res, September 1, 2001; 51(4): 647 - 658. [Full Text] [PDF]

				B. H. Ackerman, R. M. Overton, M. T. McCormick, D. D. Schocken, and D. L. Vesely Disposition of Vessel Dilator and Long-Acting Natriuretic Peptide in Healthy Humans after a One-Hour Infusion J. Pharmacol. Exp. Ther., August 1, 1997; 282(2): 603 - 608. [Abstract] [Full Text]