EXPRESSION OF ENDOTHELIN PEPTIDES AND MESSENGER-RNA IN THE HUMAN HEART

1. We have examined the expression of endothelin isoforms and their pr ecursors in the human heart using RIA, HPLC, immunocytochemistry and r everse transcriptase-polymerase chain reaction assays. 2. Highly speci fic RIAs were used to measure the levels of mature endothelin and big endothelin-1 immunoreactivity in extracts of human right ventricle, Th ere was no significant difference between samples from patients with i schaemic heart disease and idiopathic dilated cardiomyopathy. 3. HPLC coupled with RIAs allowed the separation and identification of the thr ee mature isoforms of endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1, In extracts of human endocardial endothe lial cells, peaks of immunoreactivity that co-eluted with authentic en dothelin-1, big endothelin-1 and C-terminal fragment were found. 4. In tense immunocytochemical staining of mature endothelin immunoreactivit y was detected in the cytoplasm of endothelial cells of all regions of the heart tested, Big endothelin-1 immunoreactivity mirrored that of the mature peptide and, in two of three individuals tested, big endoth elin-2 immunoreactivity was also detected, No big endothelin-3 immunor eactivity was detected in any of the tissues examined.