Effects of Indomethacin in Rabbit Renovascular Hypertension

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous inject ons (3 mg day—1 kg—1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), and ten rabbits with one-kidney Goldblatt hypertension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1·15 to 0·2 ng/ml, sem 0·2; P < 0·01) and plasma renin activity (20 to 3 ng h—1 ml—1, sem 1, P < 0·01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31·5 ng h—1 ml—1, sem 3 and 4 respectively; P < 0·01) and plasma prostaglandin E2 (1·2 to 3·4 ng/ml, sem 0·2 and 0·4 respectively; P < 0·05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7·6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, sem 7·7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, sem 4 and 6 respectively; P < 0·01) and decreased renal function (plasma creatinine 0·9 ± 0·04 to 3·5 ± 1 mg/100 ml, sem 0·04 and 1 respectively; P < 0·01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.