1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet.
2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or β-adrenoreceptor-blockade therapy.
3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy.
4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased α-adrenergic tone, which may limit the blood pressure-lowering effect of β-adrenoreceptor-blockade.
5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or β-adrenoreceptor blockers.