Ritter J M, Barrow S E, Doktor H S, Stratton P D, Edwards J S, Henry J A, Gould S
Department of Clinical Pharmacology, United Medical School, Guy's Hospital, London, UK.
Hypertension. 1993 Aug;22(2):197-203. doi: 10.1161/01.hyp.22.2.197.
Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart. On each occasion, they received two doses of either placebo or ridogrel (300 mg) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B2, 6-oxo-prostaglandin F1 alpha, and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B2 and thromboxane B2 compared with placebo (21 +/- 6 versus 279 +/- 28 and 14 +/- 4 versus 39 +/- 9 ng/g creatinine, respectively; P < .0001 and P < .05). Excretion of 2,3-dinor-6-oxoprostaglandin F1 alpha and 6-oxoprostaglandin F1 alpha was increased by ridogrel compared with placebo (184 +/- 20 versus 146 +/- 11 and 86 +/- 9 versus 58 +/- 6 ng/g creatinine, respectively; P < .05). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P < .0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure.
对16例无并发症的原发性高血压患者研究了血栓素合酶抑制剂和受体拮抗剂联合制剂利度格雷的短期效应。在停用抗高血压药物的2周安慰剂期后，患者在相隔3周的两个时间段住院过夜。每次，根据双盲交叉方案，他们每隔12小时接受两剂安慰剂或利度格雷（300毫克）。通过使用气相色谱/质谱法测量血栓素B2、6-氧代前列腺素F1α及其各自的2,3-二去甲代谢物的尿排泄量，研究肾脏和全身血栓素A2和前列环素的生物合成。用比浊法研究血小板对血栓素A2模拟物和二磷酸腺苷的反应。每隔20分钟自动测量血压。与安慰剂相比，利度格雷降低了2,3-二去甲血栓素B2和血栓素B2的排泄量（分别为21±6与279±28以及14±4与39±9纳克/克肌酐；P<.0001和P<.05）。与安慰剂相比，利度格雷使2,3-二去甲-6-氧代前列腺素F1α和6-氧代前列腺素F1α的排泄量增加（分别为184±20与146±11以及86±9与58±6纳克/克肌酐；P<.05）。利度格雷选择性地拮抗血小板对血栓素模拟物的聚集作用（P<.0001）。利度格雷治疗期和安慰剂治疗期的血压无显著差异。因此，在原发性高血压患者中，急性给予利度格雷可降低肾脏和肾外血栓素A2的生物合成，增加肾脏和肾外前列环素的生物合成，抑制血栓素受体激活的血小板聚集，但对全身动脉压无影响。
