The increase in human plasma immunoreactive endothelin but not big endothelin-1 or its C-terminal fragment induced by systemic administration of the endothelin antagonist TAK-044.

摘要: 1. We examined the effects of systemic infusion, in healthy human volunteers, endothelin antagonist TAK-044 on plasma concentrations mature endothelin, big endothelin-1 and C-terminal fragment endothelin-1, by selective solid-phase extraction specific radioimmunoassays. 2. Unlabelled competed with [125I]-endothelin-1 binding to left ventricle tissue a biphasic manner giving KD values 0.11 nM 26.8 at ETA ETB receptor subtypes, respectively, indicating 244 fold selectivity for subtype. 3. A 15 min intravenous infusion placebo or 30 mg (giving serum concentration 2 nM, calculated block > 95% but 99% 75% receptors), immunoreactive were increased 3.3 over basal levels (P < 0.01). The unchanged. 5. At both doses TAK-044, there significant decreases diastolic blood pressure, peripheral vascular resistance, corresponding increases cardiac index stroke index. There no changes systolic mean arterial pressures heart rate. 6. Since only peptide increased, we conclude that most likely sources contributing observed rise displacement receptor-bound reduction clearance rather than synthesis.