Endothelin-1 Is a Key Mediator of Coronary Vasoconstriction in Patients With Transplant Coronary Arteriosclerosis
| Autor: | James C. Fang, Peter Ganz, Eric Larose, Scott Kinlay, Dominik Behrendt, Andrew P. Selwyn |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Time Factors Endothelin A Receptor Antagonists Vasodilator Agents Vasodilation Coronary Artery Disease Peptides Cyclic Severity of Illness Index Coronary circulation Coronary Circulation Internal medicine medicine Humans Infusions Intravenous Aged Endothelin-1 Vasomotor business.industry Microcirculation Middle Aged Receptor Endothelin A Coronary arteries Transplantation medicine.anatomical_structure Vasoconstriction Case-Control Studies Vascular resistance Cardiology Heart Transplantation Female Vascular Resistance medicine.symptom Cardiology and Cardiovascular Medicine business Blood Flow Velocity Artery |
| Zdroj: | Circulation: Heart Failure. 2:409-416 |
| ISSN: | 1941-3297 1941-3289 |
| Popis: | Background— Transplant coronary arteriosclerosis (TCA) is the principal long-term complication in cardiac transplant recipients. The mediators responsible for vascular proliferation and vasoconstriction typical of TCA remain largely unknown. We tested whether endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, contributes to the pathogenesis and manifestations of TCA. Methods and Results— BQ-123, an ET-1 receptor-A antagonist, was infused into a coronary artery (40 nmol/min for 60 minutes) of 18 subjects, 6�4 years after transplantation. Vasomotor responses were measured in the infused artery and in a noninfused control artery in patients with (n=10) and without (n=8) advanced TCA (108 total coronary segments). Changes in diameters were compared at 15-minute intervals up to 60 minutes. Contribution of ET-1 to coronary constrictor tone was assessed by comparing vasodilation from BQ-123 with that of the maximal vasodilator nitroglycerin (200-μg intracoronary bolus). BQ-123 dilated coronary arteries of transplanted patients (8.4% at 60 minutes versus −0.4% in noninfused arteries, P P =0.004). Judged against the response to nitroglycerin, ET-1 accounted for 53.2% of coronary tone in advanced TCA but only 12.9% without advanced TCA. Conclusions— This study shows for the first time in humans that ET-1 is an important mediator of coronary vasoconstriction in TCA and accounts for >50% of the increased vasomotor tone. Therapeutic targeting of ET-1 may retard the development of TCA. |
| Databáze: | OpenAIRE |
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