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Pulmonary Endothelin-1 Clearance in Human Pulmonary Arterial Hypertension^*

^* From the Jewish General Hospital and Montreal Heart Institute, Montreal, QC, Canada.

Correspondence to: David Langleben, MD, Division of Cardiology, Jewish General Hospital, Room E258, 3755 Cote Ste Catherine, Montreal, QC, Canada, H3T 1E2; e-mail: david.langleben{at}mcgill.ca

Endothelin (ET)-1, the potent vasoconstrictor and smooth muscle mitogen, is a likely mediator of human pulmonary arterial hypertension (PAH). High plasma levels and intrapulmonary synthesis of ET-1 are found in various types of PAH. ET-1 is normally cleared from the pulmonary circulation via ET-B receptors found on endothelial cells. It is not known how PAH, which reduces the amount of perfused vascular surface area in the lung, affects ET-1 clearance. It is also unknown how the amount of ET-B receptor expression, which may be altered in PAH, affects ET-1 clearance. We used an indicator dilution technique to measure the levels of first-pass pulmonary extract of trace quantities of ¹²⁵I-ET-1 from circulating blood (mean [± SD] levels, 47 ± 7%). We then calculated the permeability surface product (normal range, 18 to 40 mL/s), an index of the functional vascular surface area that is available for ET-1 extraction. Patients with primary pulmonary hypertension (PPH) [n = 17] and PAH from connective tissue disease (CTD) [n = 12] were studied. For both groups, the mean ET extraction was slightly reduced (PPH patients, 39 ± 16%; CTD patients, 36 ± 16%), while the permeability surface product was reduced for most patients (PPH patients, 18 ± 10%; CTD patients, 19 ± 11%). However, 59% of patients had first-pass pulmonary extract levels within the normal range. Thus, in many patients with PAH, despite the reduced functional vascular surface area available for ET-1 clearance, high circulating ET-1 levels may relate more to excess production than to reduced clearance. The fact that ET-B receptor-mediated clearance is preserved in many patients may be of importance to the relative effectiveness of selective vs nonselective ET antagonists.

	Footnotes

 
This research was supported by the Canadian Institute of Health Research.

Abbreviations: CTD = connective tissue disease; ET = endothelin; PAH = pulmonary arterial hypertension; PPH = primary pulmonary hypertension

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Langleben, D. Articles by Caron, A. Search for Related Content PubMed PubMed Citation Articles by Langleben, D. Articles by Caron, A.