Human pulmonary circulation is an important site for both clearance and production of endothelin-1.
BACKGROUND
Animal studies suggest a major role of the pulmonary circulation in the clearance of circulating endothelin-1 (ET-1). The contribution of the human pulmonary circulation to plasma ET-1 clearance, however, has never been quantified. The absence of an AV gradient in plasma ET-1 has previously been interpreted as evidence that the lungs do not have a role in modulating circulating ET-1 levels. This study was designed to quantify and discern between pulmonary ET-1 clearance and production in humans.


RESULTS
We studied 13 subjects by combining the multiple indicator-dilution technique with the measurement of immunoreactive ET-1 (irET-1). All patients had normal left ventricular ejection fractions (61 +/- 7%, mean +/- SD) and baseline hemodynamics. Mean pulmonary ET-1 extraction was 47 +/- 7%. The ET-1 extracted does not return to circulation and can be characterized by a sequestration rate constant: Kseq = 0.048 +/- 0.019 s-1. There was no significant difference between irET-1 levels from the pulmonary artery and aorta (0.61 +/- 0.29 and 0.68 +/- 0.33 pg/mL, respectively; P = .22); the normal lung consequently produces an amount of ET-1 that is quantitatively similar to the amount that has been extracted.


CONCLUSIONS
The human lung is an important site for both clearance and production of ET-1. There is a normal physiological balance of ET-1 across the pulmonary circulation, which explains the absence of difference in AV ET-1 levels despite a 47 +/- 7% clearance. Reduced pulmonary clearance or increased production of this peptide may contribute to the increase in circulating levels found in various cardiovascular conditions.
Dupuis
J
J
Department of Medicine, Montreal Heart Institute, St. Michael's Hospital, Toronto, Canada.
Stewart
D J
DJ
Cernacek
P
P
Gosselin
G
G
D000368:Aged; D001011:Aorta; D019332:Endothelin-1 / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007201:Indicator Dilution Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D011651:Pulmonary Artery; D011652:Pulmonary Circulation
D019332:Endothelin-1