Etiology-Specific Endothelin-1 Clearance in Human Precapillary Pulmonary Hypertension
| Autor: | David Langleben, Isaac Langleben, Jean-Luc Senécal, Jocelyn Dupuis, Andrew Hirsch, Michele Giovinazzo, Murray Baron |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Hypertension Pulmonary Thermodilution Indicator Dilution Techniques Critical Care and Intensive Care Medicine Glucosides Internal medicine Humans Medicine Endothelial dysfunction Receptor Lung Endothelin-1 Cyclohexanones business.industry Microcirculation Respiratory disease medicine.disease Pulmonary hypertension Endothelin 1 Connective tissue disease medicine.anatomical_structure Cardiology Pulmonary Diffusing Capacity Female Endothelium Vascular Cardiology and Cardiovascular Medicine business Endothelin receptor |
| Zdroj: | Chest. 129:689-695 |
| ISSN: | 0012-3692 |
| DOI: | 10.1378/chest.129.3.689 |
| Popis: | Study objectives Endothelin (ET)-1 is a mediator of vascular remodeling seen in human pulmonary hypertension (PH), and it is normally cleared via endothelial ET-B receptors. Increased levels of ET-1 are found in precapillary PH, partly from increased synthesis. We hypothesized that the endothelial dysfunction and vascular remodeling seen in human precapillary PH would also reduce ET-1 clearance. Design and setting Case series from a single institutional PH center. Patients Thirty-four patients with pulmonary arterial hypertension (PAH; idiopathic [IPAH], n = 19; connective tissue disease [CTD], n = 15) and 11 patients with chronic thromboembolic PH were studied. Measurements and results Using indicator dilution methods, the first-pass extraction of radiolabeled ET-1 through the pulmonary circulation, and permeability surface (PS) area, an index of functional microvascular surface available for ET-1 clearance, were determined. Mean extraction for IPAH and thromboembolic PH groups was normal, but it was reduced in PAH from CTD; 69% of all patients studied had normal extraction. The mean PS product was reduced significantly for all three etiologies as compared to normal, but 58% of IPAH patients and 40% of CTD-related PAH patients had normal PS products. Conclusions Receptor-mediated ET-1 extraction and functional vascular surface area for clearance vary between etiologies of PAH. However, contrary to our hypothesis, endothelial ET-B receptor-mediated extraction is preserved in many patients. The scientifically significant finding of our study is that high ET-1 levels seen in patients with PAH must be predominantly due to excess synthesis rather than reduced clearance. The finding that endothelial ET-B receptors are still present and functional in PAH may also be of relevance to the choice of selective vs nonselective ET receptor antagonists. |
| Databáze: | OpenAIRE |
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