Articles |

Pulmonary Endothelin-1 Clearance in Human Pulmonary Arterial Hypertension* FREE TO VIEW

David Langleben; J. Dupuis; A. Hirsch; M. Giovinazzo; I. Langleben; J. Khoury; N. Ruel; A. Caron
Author and Funding Information

*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@mcgill.ca

Chest. 2005;128(6_suppl):622S. doi:10.1378/chest.128.6_suppl.622S-a
Text Size: A A A
Published online

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.

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




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543