ATRIAL NATRIURETIC PEPTIDES NEGATIVELY AND POSITIVELY MODULATE CIRCULATING ENDOTHELIN IN HUMANS

The present investigation was designed to examine the effect of four a trial peptide hormones with vasodilatory properties on the circulating immunoreactive (ir) levels of the vasoconstrictive peptide endothelin (ET) in 36 healthy human subjects. Circulating levels of human ET and cyclic guanosine monophosphate ([cGMP] a potential mediator of the ef fects of atrial peptides) were measured every 30 minutes during 1-hour preinfusion, 1-hour infusion, and 3-hour postinfusion periods. Atrial natriuretic factor ([ANF] amino acid (aa) 99 to 126 of the 126-aa ANF prohormone) and kaliuretic peptide (aa 79 to 98 of this same prohormo ne) significantly (P < .05) decreased circulating ET concentrations. K aliuretic peptide effects were early and ANF effects were delayed unti l kaliuretic peptide effects began to wine. Long-acting natriuretic pe ptide (LANP), consisting of aa 1 to 30 of the ANF prohormone, on the o ther hand, significantly (P < .05) increased ET circulating concentrat ions during a 1-hour infusion period; The increase in ET in the circul ation Secondary to LANP became nonsignificant, although it was still e levated, within 30 minutes of ceasing LANP infusion. Vessel dilator, c onsisting of aa 31 to 67 of the ANF prohormone, and infusion of vehicl e alone did not significantly change circulating levels of ET during t he 5 hours of this investigation. ANF infusion increased plasma cGMP s evenfold, but plasma cGMP had decreased to only onefold above normal d uring the period that ANF had an effect on circulating ET levels. Ther e was not any significant increase or decrease in plasma cGMP concentr ations secondary to the other atrial peptide hormones. These data sugg est that kaliuretic peptide and ANF negatively modulate circulating ET concentrations, while LANP, which is released simultaneously with ANF in response to physiologic stimuli, positively modulates circulating ET concentrations to help maintain circulating ET within a narrow norm al range. The data from the present investigation would further sugges t that circulating cGMP levels do not mediate the various atrial pepti de effects on circulating ET levels. Copyright (C) 1996 by W.B. Saunde rs Company