Does endothelin play a role in chemoreception during acute hypoxia in normal men?
| Autor: | Christian Melot, Marko Gujic, Anne Houssiere, Philippe van de Borne, Nathalie Denewet, Robert Naeije, Pascale Jespers, Jean-François Argacha, André Noseda, Olivier Xhaet |
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| Přispěvatelé: | Clinical sciences, Cardio-vascular diseases, Cardiology |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Endothelin Receptor Antagonists
Male Sympathetic nervous system Sympathetic Nervous System Apnea/physiopathology Apnea Peripheral chemoreceptors Blood Pressure Critical Care and Intensive Care Medicine Endothelins Receptors Endothelin/physiology Heart Rate Medicine Hypoxia Hypoxia/physiopathology Chemoreceptor Cells/physiology Sulfonamides Cross-Over Studies Receptors Endothelin Muscles Heart Rate/drug effects Chemoreceptor Cells medicine.anatomical_structure Acute Disease medicine.symptom Endothelin receptor Cardiology and Cardiovascular Medicine medicine.drug Pulmonary and Respiratory Medicine medicine.hormone Adult medicine.medical_specialty Sulfonamides/pharmacology Muscles/innervation Blood Pressure/drug effects Double-Blind Method Internal medicine Heart rate Humans Sympathetic Nervous System/drug effects business.industry Endothelins/physiology Bosentan Pulmonary Ventilation/drug effects Hypoxia (medical) respiratory tract diseases Endocrinology Reflex business Pulmonary Ventilation |
| Popis: | BACKGROUND: The peripheral chemoreceptors are the dominant reflex mechanism responsible for the rise in ventilation and muscle sympathetic nerve activity (MSNA) in response to hypoxia. Animal studies have suggested that endothelin (ET) plays an important role in chemosensitivity. Moreover, several human clinical conditions in which circulating ET levels are increased are accompanied by enhanced chemoreflex sensitivity. Whether ET plays a role in normal human chemosensitivity is unknown. METHODS: We determined whether bosentan, a nonspecific ET receptor antagonist, would decrease chemoreflex sensitivity in 14 healthy subjects. We assessed the effects of bosentan on the response to isocapnic hypoxia, using a randomized, crossover, double-blinded study design. RESULTS: Bosentan increased mean (+/- SEM) plasma ET levels from 1.97 +/- 0.28 to 2.53 +/- 0.23 pg/mL (p = 0.01). Hypoxia increased mean minute ventilation from 6.7 +/- 0.3 to 8+/0.4 L/min (p < 0.01), mean MSNA from 100 to 111 +/- 5% (p < 0.01), mean heart rate from 67 +/- 3 to 86 +/- 3 beats/min (p < 0.01), and mean systolic BP from 116 +/- 3 to 122 +/- 3 mm Hg (p < 0.01). However, none of these responses differed between therapy with bosentan and therapy with placebo (p = 0.26). Bosentan did not affect the mean MSNA responses to the apneas, during normoxia (change from baseline: placebo, 259 +/- 58%; bosentan, 201 +/- 28%; p = 0.17) or during hypoxia (change from baseline: placebo, 469 +/- 139%; bosentan, 329 +/- 46%; p = 0.24). The durations of the voluntary end-expiratory apneas in normoxia and hypoxia, and the subsequent reductions in oxygen saturation, were also similar with therapy using bosentan and placebo (p = 0.42). CONCLUSION: In healthy men, ET does not play an important role in peripheral chemoreceptor activation by acute hypoxia. |
| Databáze: | OpenAIRE |
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