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. (Tue,) conducted a 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).