title: Effect of angiotensin-converting enzyme inhibitors on glomerular eicosanoid production in normotensive and spontaneously hypertensive rats.
abstract: 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 less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Renal Research Laboratories, School of Postgraduate Medicine and Biological Sciences, University of Keele, Staffordshire, U.K.
authors.forename: P
authors.initials: P
authors.lastname: Harding
authors.forename: C
authors.initials: C
authors.lastname: Stonier
authors.forename: G M
authors.initials: GM
authors.lastname: Aber
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D046508:Culture Techniques; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis*; D004656:Enalapril / Q000494:pharmacology; D017328:Fosinopril; D006973:Hypertension / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013928:Thromboxane A2 / Q000096:biosynthesis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015777:Eicosanoids; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D004656:Enalapril; D011392:Proline; D002216:Captopril; D015232:Dinoprostone; D017328:Fosinopril