title: Mechanisms underlying impairment of endothelium-dependent relaxation by fetal bovine serum in organ-cultured rat mesenteric artery.
abstract: Organ culture of blood vessels provides a useful technique to investigate long-term effects of drugs because tissue architecture and function are well preserved. Various growth factors are responsible for structural and functional changes during vascular diseases. We investigated long-term effects of fetal bovine serum (FBS) which contains such factors on endothelium-dependent relaxation using organ-culture method. Rat isolated mesenteric arteries with endothelium were cultured for 3 days without or with 10% FBS (FBS). Acetylcholine- and bradykinin-induced endothelium-dependent relaxations were significantly impaired in FBS, whereas sodium nitroprusside-induced relaxation of endothelium-removed artery was unchanged. Morphological examination revealed that endothelium was intact in FBS. Acetylcholine-induced nitric oxide (NO) release as detected by 4, 5-diaminofluorescein significantly decreased in FBS, whereas endothelial NO synthase expression was unchanged. A Ca(2+) ionophore, A23187-induced relaxation was unchanged in FBS. A phospholipase C activator, m-3M3FBS-induced relaxation of FBS was unchanged in either Ca(2+)-containing or -free solution. Total expressions of transient receptor potential canonical channels (TRPCs: TRPC-1, -4, -5) were similar in FBS. These data suggest that FBS impairs endothelium-dependent relaxation by inhibiting events upstream of phospholipase C activation including phospholipase C, G-protein, and receptors in endothelium.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Morita
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002417:Cattle; D003470:Culture Media / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D044967:Serum; D013449:Sulfonamides / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D000096926:Benzenesulfonamides
chemical_list: D000109:Acetylcholine; D001920:Bradykinin; D000001:Calcimycin; D061207:Calcium Ionophores; D003470:Culture Media; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside; D013449:Sulfonamides; D050052:TRPC Cation Channels; D010738:Type C Phospholipases; C473783:2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide; D000096926:Benzenesulfonamides