Effects of intrapericardially administered endothelin-1 on pericardial natriuretic peptide concentrations of the in situ dog heart

It has recently been proposed that endothelin-1 (ET-1) is an important activator of natriuretic peptide atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP)] release in the heart and may mediate ANP and BNP deliberation to myocardial stretch and ischemia. The close inter-relationship between ET-1 and natriuretic peptide release was indicated mainly by the results of in vitro studies. In vivo, the local alterations of ANP and BNP levels in the myocardial interstitium can be well characterized by the changes of their pericardial fluid concentrations. The effect of the intrapericardially administered ET-1 on natriuretic peptide concentrations was studied on the in situ dog heart (n = 8). Control and three consecutive infusate samples were removed from the pericardial sac following ET-1 administration (150 pmol/kg) and parallel peripheral blood samples were taken to determine the ANP and BNP concentrations (enzyme-linked immunosorbent assay). Standard hemodynamic parameters were recorded continuously. In our results the intrapericardial ET-1 increased pericardial ANP but not BNP concentrations significantly (control versus ANPmax, 37 +/- 5 ng/mL versus 94 +/- 12 ng/mL; P < 0.02). ET-1 elicited significant ST elevations without changes of the hemodynamic values and the natriuretic peptide levels in the arterial plasma samples. In conclusion, intrapericardial ET-1 effectively stimulated the myocardial ANP release, which was reflected as elevation in the pericardial ANP level. The results also support the hypothesis that important regulatory mechanisms might be activated from the pericardium.