title: Endothelium-derived relaxing factor-mediated vasodilation in mouse mesenteric vascular beds.
abstract: The endothelium in rat mesenteric vascular beds has been demonstrated to regulate vascular tone by releasing mainly endothelium-derived hyperpolarizing factor (EDHF), which is involved in the activation of K(+) channels and gap-junctions. However, it is unclear whether the endothelial system in mouse resistance arteries contributes to regulation of the vascular tone. The present study was designed to investigate the role of the endothelium using acetylcholine and A23187 (Ca(2+) ionophore) in mesenteric vascular beds isolated from male C57BL/6 mice and perfused with Krebs solution to measure perfusion pressure. In preparations with active tone produced by methoxamine in the presence of guanethidine, injections of acetylcholine, A23187, and sodium nitroprusside (SNP) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. The vasodilator responses to acetylcholine and A23187, but not SNP, were abolished by endothelium dysfunction and significantly inhibited by N(ω)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) and tetraethylammonium (K(+)-channel inhibitor) but not glibenclamide (ATP-sensitive K(+)-channel inhibitor). Indomethacin (cyclooxygenase inhibitor) significantly blunted only A23187-induced vasodilation, while 18α-glycyrrhetinic acid (gap-junction inhibitor) attenuated only acetylcholine-induced vasodilation. These results suggest that the endothelium in mouse mesenteric arteries regulates vascular tone by prostanoids, EDHF, and partially by nitric oxide, different from the endothelium of rat mesenteric arteries.
authors.affiliation: Department of Clinical Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Wake
authors.forename: Narumi
authors.initials: N
authors.lastname: Hashikawa-Hobara
authors.forename: Kento
authors.initials: K
authors.lastname: Makino
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D061207:Calcium Ionophores; D016861:Cyclooxygenase Inhibitors; D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C119129:18alpha-glycyrrhetinic acid; D009599:Nitroprusside; D000001:Calcimycin; D019789:Tetraethylammonium; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D006034:Glycyrrhetinic Acid; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin