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Vessel dilator, long acting natriuretic peptide, and kaliuretic peptide increase circulating prostaglandin E2
D L Vesely1, G I Perez-Lamboy, D D Schocken
1Department of Medicine, University of South Florida Health Sciences Center and James A. Haley Veterans Hospital, Tampa 33612, USA. VESELY.DAVID_L@TAMPA.VA.GOV
Insights
Three atrial natriuretic peptides, including vessel dilator and long-acting natriuretic peptide, significantly increase prostaglandin E2 (PGE2) levels in individuals with congestive heart failure (CHF). This suggests these peptides may contribute to elevated PGE2 in CHF.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Biochemistry
Background:
- Prostaglandin E2 (PGE2) levels are elevated in congestive heart failure (CHF) patients, but the underlying cause remains unclear.
- Prostaglandins require synthesis stimulation and are not stored, implying hormonal or substance triggers in CHF.
- Four peptide hormones derived from the atrial natriuretic peptide (ANP) prohormone share similar biological properties with PGE2.
Purpose of the Study:
- To investigate whether three specific atrial natriuretic peptides (long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide) increase circulating PGE2 concentrations in CHF patients.
- To determine the magnitude and duration of PGE2 elevation induced by these peptides.
Main Methods:
- Infusion of long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide at 100 ng/kg/min for 60 minutes in CHF patients.
- Measurement of PGE2 concentrations in circulation before, during, and after peptide infusions.
- Statistical analysis to determine the significance of observed changes in PGE2 levels.
Main Results:
- Vessel dilator caused an 8-fold increase in PGE2 within 20 minutes, with sustained elevation.
- Long-acting natriuretic peptide induced a maximal 27-fold increase in PGE2.
- Kaliuretic peptide demonstrated a delayed but prolonged effect, increasing PGE2 for two hours post-infusion.
Conclusions:
- Three endogenous atrial natriuretic peptides (long-acting natriuretic peptide, vessel dilator, kaliuretic peptide) stimulate PGE2 synthesis and release into circulation.
- These peptide hormones may partially explain the elevated PGE2 levels observed in patients with congestive heart failure.
Abstract:
Prostaglandin E2 (PGE2) increases in the circulation of persons with congestive heart failure (CHF), but the cause of this increase is unknown. Prostaglandins are not stored, therefore, they cannot be released in response to congestive heart failure itself but rather need to have their synthesis stimulated by a hormone or some other substance. Prostaglandin E2's biologic properties are nearly identical to four peptide hormones originating from amino acids 1-30 [long acting natriuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic peptide, ANP] of the 126 amino acid ANP prohormone. ANP previously has been found to have no effect on circulating PGE2 concentrations in persons with CHF. The present investigation was designed to determine if one or more of the other three atrial natriuretic peptides might increase PGE2 when infused at their respective 100 ng/kg body weight/minute concentrations for 60 minutes in persons with congestive heart failure. Vessel dilator increased PGE2 8-fold (P<0.001) in the first 20 minutes of its infusion with PGE2 remaining 2-3 fold increased (P<0.05) for 60 minutes after stopping its infusion. Long acting natriuretic peptide did not increase PGE2 until 40 minutes of its infusion but it caused the maximal increase (27-fold; P<0.001) of PGE2 of the three peptide hormones tested. Kaliuretic peptide's stimulated increase of PGE2 also began in a delayed fashion but its effects lasted the longest, with PGE2 being increased (P<0.05) for two hours after the cessation of kaliuretic peptide's infusion. This investigation demonstrates that 1) three endogenous peptide hormones increase PGE2 in the circulation and 2) suggests that the known increase in PGE2 in CHF may be in part secondary to these peptides.