title: Dietary eicosapentaenoic acid does not modify cyclosporin-induced inhibition of angiotensin II-stimulated prostaglandin synthesis in mesangial cells.
abstract: Clinical and experimental cyclosporin A (CSA) nephrotoxicity is characterized by alterations in renal hemodynamics and a reduction in glomerular filtration rate (GFR). The mesangial cell may be a target for the actions of CSA. CSA has been shown to activate the renin angiotensin system and to increase the excretion of TXB2 (the stable metabolite of TXA2). This study investigated the role of CSA and mesangial cell prostaglandin release in mediating some of the alterations in renal hemodynamics. Primary rat mesangial cell cultures (first passage) were exposed to CSA followed by stimulation with angiotensin II (AII) 10(-7) M. PGE2 and TXB2 release was measured after 5 and 15 minutes incubation. Experimental CSA nephrotoxicity in rats has been shown to be reduced by the use of MaxEPA fish oil (containing eicosapentaenoic acid) as the vehicle for CSA. Therefore, the experiments were repeated using mesangial cells obtained from rats fed an enriched eicosapentaenoic acid (MaxEPA) diet for 3 weeks. CSA significantly inhibited AII stimulated PGE2 release in both experiments. There was no increase in TXB2 release. Alterations in membrane fatty acid composition, available for prostaglandin synthesis, did not alter the results. This study demonstrated that CSA significantly inhibits AII-stimulated prostaglandin release. The increased excretion of TXB2, seen with CSA treatment, does not arise from the mesangial cells, and the protective effect of MaxEPA, as a vehicle for CSA, is not due to its effects on mesangial cell prostaglandin release.
authors.affiliation: Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Walker
authors.forename: V A
authors.initials: VA
authors.lastname: Lazzaro
authors.forename: G G
authors.initials: GG
authors.lastname: Duggin
authors.forename: J S
authors.initials: JS
authors.lastname: Horvath
authors.forename: D J
authors.initials: DJ
authors.lastname: Tiller
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D003524:Cyclosporins / Q000009:adverse effects*; D004032:Diet; D015232:Dinoprostone / Q000096:biosynthesis; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000096:biosynthesis
chemical_list: D001095:Arachidonic Acids; D003524:Cyclosporins; D011453:Prostaglandins; D013931:Thromboxanes; D000804:Angiotensin II; D015232:Dinoprostone