Greater functional ETB receptor antagonism with bosentan than sitaxsentan in healthy men
| Autor: | David J. Webb, Jane Goddard, Pajaree Lilitkarntakul, Vanessa Melville, Neeraj Dhaun, Iain M. MacIntyre |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Endothelin A Receptor Antagonists Administration Oral Vasodilation Blood Pressure Thiophenes Pharmacology Placebo Drug Administration Schedule Young Adult Double-Blind Method Reference Values medicine.artery Internal Medicine medicine Humans Brachial artery Antihypertensive Agents Probability Analysis of Variance Sulfonamides Cross-Over Studies Dose-Response Relationship Drug Endothelin-1 business.industry Antagonist Blood Pressure Determination Bosentan Isoxazoles Middle Aged Receptor Endothelin A Crossover study Blockade Plethysmography Endothelin receptor business medicine.drug |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 55(6) |
| ISSN: | 1524-4563 |
| Popis: | Endothelin (ET)-1 is implicated in the development of hypertension and a role for endothelin receptor antagonists (ETRAs) in the management of hypertension is emerging. ETRAs are classified as selective or mixed depending on their degree of ET A :ET B receptor blockade. As yet, there are no comparative studies in humans that measure biochemical and functional ET B blockade achieved by currently licensed ETRAs. We therefore investigated the effects of bosentan, a mixed ETRA, and sitaxsentan, an ET A selective ETRA, on plasma ET-1 concentrations and ET B -mediated vasodilatation to ET-3. In a randomized, double-blind, 3-way crossover study, 10 healthy subjects received 7 days of placebo, bosentan 250 mg, and sitaxsentan 100 mg daily. Plasma ET-1 concentrations were measured at baseline and 3 hours on day 1 and predose on day 7. Subjects also underwent forearm blood flow measurements on day 7 of each period with brachial artery infusion of ET-3 (60 pmol/min for 5 minutes). Bosentan, but not placebo or sitaxsentan, significantly increased plasma ET-1 concentrations at day 7 (+0.70±0.20 pg/mL; P P A/B antagonist bosentan, but not the selective ET A antagonist sitaxsentan, causes functional ET B blockade at clinically relevant doses in healthy human subjects. |
| Databáze: | OpenAIRE |
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