(Circulation. 1996;94:1578-1584.)
© 1996 American Heart Association, Inc.
Articles |
Human Pulmonary Circulation Is an Important Site for Both Clearance and Production of Endothelin-1
the Department of Medicine, Montreal Heart Institute, St. Michael's Hospital, Toronto, and the Royal Victoria Hospital, Montreal, Canada.
Correspondence to Jocelyn Dupuis, MD, Montreal Heart Institute, 5000 Belanger St, Montreal, Quebec H1T 1C8, Canada.
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.
Methods and 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.
Key Words: endothelin • circulation • metabolism • endothelium
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