1. A within-patient randomized double-blind crossover study was performed on mechanisms of action of bendrofluazide in mild essential hypertension. Significant reductions in lying, standing and post-exercise blood pressure were seen after both 3 days and 10 weeks treatment with bendrofluazide (10 mg daily). 2. Plasma levels of 6-oxo-prostaglandin F 1α , the chemical hydrolysis product of prostacyclin, were significantly increased by both 3 days and 10 weeks therapy with bendrofluazide. This raises the possibility that thiazides may reduce peripheral resistance by increasing prostacyclin biosynthesis.
1. Pharmacologically active mediators of inflammation were obtained from suction bullae raised on normal and inflamed human abdominal skin. These contained a clear inflammatory exudate, which was analysed for known mediators of inflammation. 2. The exudates were examined for smooth muscle-contracting activity by a superfusion cascade bioassay, for prostaglandin F 2α by radioimmunoassay and by Lipidex 5000 gel-partition chromatography for other prostaglandins and related compounds. 3. Tetrahydrofurfuryl nicotinate (Trafuril) was applied topically before and after systemic administration of aspirin. Trafuril alone caused a sustained inflammatory response within minutes of application, which was reduced by prior administration of aspirin (a known prostaglandin synthetase inhibitor). 4. Exudate from inflamed skin showed increased prostaglandin activity compared with exudate from contralateral non-inflamed skin. However, aspirin prevented this increase in prostaglandin activity. Analysis by thin-layer and gas—liquid chromatography further suggested that Trafuril-induced inflammation was mediated by certain prostaglandins and related compounds. 5. No evidence was obtained to suggest any change in histamine or bradykinin after Trafuril. We suggest that the response caused by Trafuril is mediated by increased synthesis of prostaglandins. Aspirin, by blocking prostaglandin synthesis, prevents or reduces the erythema.