Ventricular expression of atrial natriuretic peptide after orthotopic cardiac transplantation

In order to determine if atrial natriuretic peptide is produced by the human ventricle after transplantation, specimens were obtained from 54 separate right ventricular endomyocardial biopsies from 14 transplant recipients (age range 10-19 years) and were analyzed with simultaneous plasma samples. Radioimmunoassay techniques were used to determine plasma and tissue levels of atrial natriuretic peptide in each biopsy specimen, and blot hybridizations with the atrial natriuretic peptide c deoxyribonucleic acid probe were performed once for each patient. Mean plasma levels of atrial natriuretic peptide were obtained from the right ventricle (106 +/- 12 pg/ml); there was a positive correlation with end diastolic pressure (r = 0.7, P < 0.0001). Plasma levels, however, were not significantly increased during rejection episodes. Atrial natriuretic peptide was detectable in all ventricular biopsy specimens--mean 989 +/- 164 pg/mg soluble protein. Mean tissue level during rejection episodes was 1163 +/- 17 and following treatment of rejection was 411 +/- 147--however, this difference was not significant (P = 0.55). In 6 patients biopsied within 1 month of transplantation initial myocardial levels were significantly higher than those obtained at the following biopsy (P < 0.05). Despite these initially high tissue levels no correlation was found with time posttransplantation. Ventricular tissue levels positively correlated with systolic ventricular pressure, r = 0.3, P < 0.05, but there was no significant correlation with other hemodynamic parameters. The normalized atrial natriuretic peptide messenger ribonucleic acid signal from the slot blot hybridization was 59 +/- 6 mm (peak height of signal intensity) range 20-110 mm. The expression of atrial natriuretic peptide gene was also confirmed by Northern blot analysis. The ventricular messenger ribonucleic acid signal contained a single hybridizing band of approximately 920 nucleotides. Thus, we have demonstrated that atrial natriuretic peptide production by the human ventricle is independent of innervation. The consistent atrial natriuretic peptide gene expression and detection by radioimmunoassay in apparently healthy ventricles was unexpected but may reflect the use of immunosuppressive drugs, or perhaps subclinical graft dysfunction.