Effect of furosemide on renal prostaglandins E₂ and F₂(α) in normal subjects and in patients with essential hypertension

The urinary excretion of prostaglandins (PG) E₂ and F₂(α), which reflects the renal synthesis of these substances, was evaluated by radioimmunoassay before and after an i.v. injection of furosemide in 10 normal subjects and in 10 patients with essential hypertension. In most normal subjects, urinary PGE₂ increased after furosemide injection, whereas PGF₂(α) decreased to undetectable levels. In the hypertensive subjects, PGE₂ increased to a lesser degree or decreased, but PGF₂(α) excretion was unchanged or augmented. These results suggest that furosemide may increase PGE₂ synthesis not only by increasing the availability of the substrate arachidonic acid or by inhibiting the action of the catabolizing enzyme 15-hydroxyl-PG-dehydrogenase, as has been proposed, but also by depressing the activity of the enzyme PGE₂-9-ketoreductase, which catalyzes the conversion of PGE₂ to PGF₂(α). In essential hypertension, an increased activity of PGE₂-9-ketoreductase could explain the decreased levels of PGE₂ that have recently been described in these patients. Whether these abnormalities in PG interconversion play a role in the pathogenesis of the hypertensive state or are secondary to it remains a question for further investigation.