24-HOUR PATTERN OF ATRIAL-NATRIURETIC-PEPTIDE IN HEART-TRANSPLANTATION - EVIDENCE FOR LACK OF CIRCADIAN-RHYTHM - TEMPORAL INTERRELATIONSHIPS WITH PLASMA-RENIN ACTIVITY, ALDOSTERONE AND CORTISOL

We have investigated the circadian rhythm of plasma atrial natriuretic peptide in 13 stable output heart transplanted patients, all without evidence of histological rejection and cardiac impairment, following antirejection therapy with Cyclosporine, Azathioprine and Prednisone. The 24-h pattern of plasma renin activity, plasma aldosterone and plasma cortisol has been studied as well. All the investigated variables were assayed six times over the 24-h span. The circadian time-qualified data were analyzed by ANOVA and Cosinor method. The 24-h mean levels of atrial natriuretic peptide, plasma renin activity and plasma aldosterone are significantly increased, while the concentrations of plasma cortisol are reduced in the heart transplanted recipients. ANOVA detected a significant within-day variability of all these humoral variables only in healthy subjects. A statistically significant circadian rhythm was validated by Cosinor procedure for all the investigated molecules in healthy subjects but not in heart transplanted patients. In our opinion, the increase of atrial natriuretic peptide is a counterregulatory mechanism aimed to compensate the cyclosporine-mediated activation of the renin-angiotensin-aldosterone system. The disappearance of the plasma renin activity, aldosterone and atrial natriuretic peptide circadian rhythm can be ascribed to the constant activation of the renin-angiotensin-aldosterone system. The hypocortisolism is due, in our opinion, both to glucocorticoid therapy and increase of plasma ANP concentration.