The human pulmonary circulation extracts 47% of circulating endothelin-1 and produces a similar amount, yielding no significant difference between pulmonary artery and aortic levels (P=0.22).
Observational (n=13)
The human lung is an important site for both clearance and production of endothelin-1, maintaining a physiological balance across the pulmonary circulation.
Absolute Event Rate: 0.61% vs 0.68%
p-value: p=0.22
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.
Dupuis et al. (1996) conducted an observational in Normal left ventricular ejection fraction and baseline hemodynamics (n=13). Multiple indicator-dilution technique was evaluated on Difference between immunoreactive ET-1 levels from the pulmonary artery and aorta (p=0.22). The human pulmonary circulation extracts 47% of circulating endothelin-1 and produces a similar amount, yielding no significant difference between pulmonary artery and aortic levels (P=0.22).