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Atrial natriuretic peptides negatively and positively modulate circulating endothelin in humans
D L Vesely1, S Chiou, M A Douglass
1Department of Internal Medicine, University of South Florida for Health Sciences, Tampa, FL, USA.
Insights
Four atrial peptide hormones were studied for their effects on endothelin (ET) levels. Atrial natriuretic factor (ANF) and kaliuretic peptide decreased ET, while long-acting natriuretic peptide (LANP) increased it, suggesting a regulatory role.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Peptide Hormone Research
Background:
- Atrial peptide hormones possess vasodilatory properties.
- Endothelin (ET) is a potent vasoconstrictive peptide.
- The interplay between atrial peptides and ET in human circulation requires elucidation.
Purpose of the Study:
- To investigate the impact of four specific atrial peptide hormones on circulating endothelin (ET) levels in healthy humans.
- To explore the potential role of cyclic guanosine monophosphate (cGMP) as a mediator in these interactions.
Main Methods:
- Thirty-six healthy subjects underwent controlled infusions of atrial natriuretic factor (ANF), kaliuretic peptide, long-acting natriuretic peptide (LANP), vessel dilator, or vehicle.
- Circulating levels of immunoreactive endothelin (ir-ET) and cyclic guanosine monophosphate (cGMP) were measured at regular intervals over a 5-hour period (1-hour preinfusion, 1-hour infusion, 3-hour postinfusion).
- Statistical analysis (P<.05) was employed to determine significant changes in peptide concentrations.
Main Results:
- Atrial natriuretic factor (ANF) and kaliuretic peptide significantly decreased circulating ET concentrations, with kaliuretic peptide acting early and ANF later.
- Long-acting natriuretic peptide (LANP) significantly increased circulating ET concentrations during infusion, with levels returning towards baseline post-infusion.
- Vessel dilator and vehicle infusions did not significantly alter ET levels; ANF increased plasma cGMP sevenfold, but cGMP did not correlate with ET changes mediated by other peptides.
Conclusions:
- Kaliuretic peptide and ANF exert a negative modulatory effect on circulating ET levels.
- LANP positively modulates circulating ET concentrations, potentially contributing to maintaining ET within a normal range.
- Circulating cGMP levels do not appear to mediate the observed effects of atrial peptides on ET.
Abstract:
The present investigation was designed to examine the effect of four atrial 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 effects 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 prohormone) significantly (P<.05) decreased circulating ET concentrations. Kaliuretic peptide effects were early and ANF effects were delayed until kaliuretic peptide effects began to wane. Long-acting natriuretic peptide (LANP), consisting of aa 1 to 30 of the ANF prohormone, on the other hand, significantly (P<.05) increased ET circulating concentrations during a 1-hour infusion period. The increase in ET in the circulation secondary to LANP became nonsignificant, although it was still elevated, within 30 minutes of ceasing LANP infusion. Vessel dilator, consisting of aa 31 to 67 of the ANF prohormone, and infusion of vehicle alone did not significantly change circulating levels of ET during the 5 hours of this investigation. ANF infusion increased plasma cGMP sevenfold, but plasma cGMP had decreased to only onefold above normal during the period that ANF had an effect on circulating ET levels. There was not any significant increase or decrease in plasma cGMP concentrations secondary to the other atrial peptide hormones. These data suggest 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 normal range. The data from the present investigation would further suggest that circulating cGMP levels do not mediate the various atrial peptide effects on circulating ET levels.