ENDOTHELIN PARTICIPATES IN INCREASED CIRCULATING ATRIAL-NATRIURETIC-PEPTIDE EARLY AFTER HUMAN HEART-TRANSPLANTATION

Background: Hemodynamic improvement after heart transplantation is exp ected 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 r esponse to heart transplantation. Methods: To investigate whether endo thelin may induce ANP increase in heart transplant recipients, we moni tored daily ANP, endothelin, and related hormonal, biologic, and hemod ynamic 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 vasopr essin 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-aldost erone 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 f urther increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01) a fter transplantation. Positive correlations were observed between endo thelin, isoproterenol dose, creatinine, right atrial pressure, and ANP , but multiple correlation analysis showed the important role of endot helin (r = 0.69, p < 0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001). Conclusions: Elevated endothelin, sug gesting vascular dysfunction, likely contributes to the ANP increase o bserved early after heart transplantation. Furthermore, ANP, through a cardiac endothelium feedback, may act in the maintenance of circulato ry homeostasis in heart transplant recipients.