1. This study was designed to examine the production of certain eicosanoids (prostaglandin E2), prostacyclin (as 6-keto-prostaglandin F1-alpha) and thromboxane A2 (as thromboxane B2) by glomeruli isolated from normotensive Wistar-Kyoto and spontaneously hypertensive rats both before and after the administration of one of three angiotensin-converting enzyme inhibitors, captopril, enalapril or fosinopril, for 10 days. 2. Measurements of glomerular eicosanoid production were made under basal conditions and in the presence of excess exogenous arachidonic acid. 3. The production of prostaglandin E2, 6-keto-prostaglandin F1-alpha and thromboxane B2 was greater by glomeruli from untreated spontaneous hypertensive rats (prostaglandin E2 2.24 +/- 0.41, 6-keto-prostaglandin F1-alpha 1.20 +/- 0.13 and thromboxane B2 2.75 +/- 0.43 ng 10 min-1 mg-1 of protein) than by those from Wistar-Kyoto rats (prostaglandin E2 1.41 +/- 0.28, 6-keto-prostaglandin F1-alpha 0.98 +/- 0.11 and thromboxane B2 1.29 +/- 0.24 ng 10 min-1 mg-1 of protein) under basal conditions. However, these differences only achieved statistical significance for thromboxane B2 (P < 0.01). Similar strain-related differences were noted in the presence of arachidonic acid. 4. The ratio of glomerular (prostaglandin E2 + prostacyclin)/thromboxane A2 production was significantly lower in spontaneously hypertensive rats than in their normotensive counterparts under basal conditions with values of 1.3 +/- 0.18 and 2.2 +/- 0.20, respectively (P < 0.01). 5. Angiotensin-converting enzyme inhibitors induced significant changes in the glomerular production of some eicosanoids, which differed both between strains and with the nature of the inhibitor. 6. All three angiotensin-converting enzyme inhibitors increased the ratio of glomerular (prostaglandin E2 + prostacyclin)/thromboxane A2 production in both strains of rat. This only achieved statistical significance in Wistar-Kyoto rats after treatment with enalapril (from 2.2 +/- 0.20 to 5.3 +/- 0.83, P < 0.01) and fosinopril (from 2.2 +/- 0.20 to 7.9 +/- 1.68, P < 0.01), and in spontaneously hypertensive rats after treatment with fosinopril (from 1.3 +/- 0.18 to 4.2 +/- 0.50, P < 0.005). 7. None of the angiotensin-converting enzyme inhibitors induced any change in the systolic blood pressure of Wistar-Kyoto rats, whereas captopril, enalapril and fosinopril induced significant and comparable reductions in that of spontaneously hypertensive rats from mean pretreatment values of 167.8 +/- 3.2, 164.7 +/- 2.5 and 175.2 +/- 4.0 mmHg to 150.3 +/- 2.7, 141.0 +/- 2.2 and 154.0 +/- 3.4 mmHg, respectively (P < 0.0005). 8. The effects of angiotensin-converting enzyme inhibitors on eicosanoid production by glomeruli from Wistar-Kyoto rats and spontaneously hypertensive rats appear to be unrelated to changes in systemic blood pressure or to the presence of a thiol group.
