Thromboxane A2 receptor antagonism and synthase inhibition in essential hypertension.

Abstract

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.

• Authors: J M Ritter, S E Barrow, H S Doktor, P D Stratton, J S Edwards, J A Henry, S Gould
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 22 Issue 2 Pg. 197-203 (Aug 1993) ISSN: 0194-911X [Print] United States
• PMID: 8340155 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Eicosanoids
• Pentanoic Acids
• Platelet Aggregation Inhibitors
• Pyridines
• Receptors, Thromboxane
• Thromboxane B2
• Thromboxane-A Synthase
• ridogrel

Topics

• Adult
• Aged
• Blood Pressure (drug effects)
• Double-Blind Method
• Eicosanoids (urine)
• Female
• Humans
• Hypertension (drug therapy, metabolism, physiopathology)
• Male
• Middle Aged
• Pentanoic Acids (blood, therapeutic use)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (therapeutic use)
• Pyridines (blood, therapeutic use)
• Receptors, Thromboxane (antagonists & inhibitors)
• Thromboxane B2 (blood)
• Thromboxane-A Synthase (antagonists & inhibitors)