In reply
Dr McMillen's comments emphasize a critical point in the study of endothelin (ET)—or dare we say ET-1?—in human plasma.
He mentions, "All available evidence suggests that injured blood vessels produce more endothelin and less nitric oxide than healthy blood vessels." We should become more specific in using the word endothelin: perhaps ET-1, ET-2, and ET-3, or big ET-1, big ET-2, big ET-3, and so on. Because ET-1 is only 1 member of that family of peptides and the most studied, we can only hope that he meant ET-1. Precise measurements of ET-1 in human plasma become difficult because of these various isoforms and precursors; hence, cross-reaction becomes unavoidable. The high levels obtained in some of these reports could be a result of cross-reactivity of the peptides to the various isoforms or precursors.