THROMBOXANE-A2 RECEPTOR ANTAGONISM AND SYNTHASE INHIBITION IN ESSENTIAL-HYPERTENSION

Short-term effects of ridogrel, a combined thromboxane synthase inhibi tor and receptor antagonist, were investigated in 16 patients with unc omplicated essential hypertension. After a 2-week placebo period witho ut antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart. On each occasion, they rece ived two doses of either placebo or ridogrel (300 mg) 12 hours apart a ccording to a double-blind crossover protocol. Renal and systemic thro mboxane A2 and prostacyclin biosynthesis were investigated by measurin g urinary excretion of thromboxane B2, 6-oxo-prostaglandin F1alpha, an d 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 pressur e 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 F1alpha and 6-oxoprostaglandin F1alpha was increase d by ridogrel compared with placebo (184 +/- 20 versus 146 +/- 11 and 86 +/- 9 versus 58 +/- 6 ng/g creatinine, respectively; P<.05). Ridogr el selectively antagonized platelet aggregation to the thromboxane mim etic (P<.0001). Blood pressure did not differ significantly between ri dogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extr arenal thromboxane A2 biosynthesis, increases renal and extrarenal pro stacyclin biosynthesis, inhibits thromboxane receptor-activated platel et aggregation, but has no effect on systemic arterial pressure.