Endothelin participates in increased circulating atrial natriuretic peptide early after human heart transplantation.
BACKGROUND
Hemodynamic improvement after heart transplantation is expected to normalize the neuroendocrine balance, but circulating atrial natriuretic peptide (ANP) remains elevated. Endothelin stimulates ANP secretion and its concentration increases after heart transplantation, suggesting a role for this peptide in the cardiovascular adaptative response to heart transplantation.


METHODS
To investigate whether endothelin may induce ANP increase in heart transplant recipients, we monitored daily ANP, endothelin, and related hormonal, biologic, and hemodynamic parameters before and during the first week after either heart transplantation (n = 15) or coronary artery bypass grafting (n = 10).


RESULTS
Surgery induced a transient secretory peak of arginine vasopressin and endothelin in both groups at day 1. Bypass grafting did not modify normal ANP (11.8 +/- 2.1 pmol/L), endothelin (2.4 +/- 0.3 pmol/L), renin activity (0.11 +/- 0.04 pmol/L/sec), or aldosterone (492 +/- 122 pmol/L) values. Heart transplantation normalized the renin-aldosterone axis, but the early decrease observed for ANP (from 27.2 +/- 4.8 to 21.14 +/- 1.4 pmol/L) was only partial and transient. Endothelin further increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01) after transplantation. Positive correlations were observed between endothelin, isoproterenol dose, creatinine, right atrial pressure, and ANP, but multiple correlation analysis showed the important role of endothelin (r = 0.69, p < 0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001).


CONCLUSIONS
Elevated endothelin, suggesting vascular dysfunction, likely contributes to the ANP increase observed early after heart transplantation. Furthermore, ANP, through a cardiac endothelium feedback, may act in the maintenance of circulatory homeostasis in heart transplant recipients.
Geny
B
B
Laboratoire d'Explorations Fonctionnelles du Système Circulatoire, Université Louis Pasteur, Strasbourg, France.
Piquard
F
F
Follenius
M
M
Thiranos
J C
JC
Charpentier
A
A
Epailly
E
E
Levy
F
F
Kretz
J G
JG
Eisenmann
B
B
Haberey
P
P
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D001026:Coronary Artery Bypass; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D005260:Female; D016027:Heart Transplantation; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D016232:Endothelins; D009320:Atrial Natriuretic Factor