title: The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation.
abstract: Endothelium-dependent relaxations are achieved by a combination of endothelium-derived prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). However, it remains to be fully clarified whether the relative contribution of these three mechanisms to endothelium-dependent relaxations varies as a function of the vessel size. This study was designed to clarify this point. Acetylcholine (ACh)-induced endothelium-dependent relaxations were examined in isolated blood vessels taken from the aorta and the proximal and distal mesenteric arteries of the rat. The contributions of PGI2, NO, and EDHF were evaluated by the inhibitory effects of indomethacin, N omega-nitro-L-arginine methyl ester (L-NAME) in the presence of indomethacin, and KCl in the presence of indomethacin and L-NAME, respectively. The membrane potentials were recorded with microelectrodes. The expression of endothelial No synthase (eNOS) was examined by both immunostaining and immunoblotting. The contribution of PGI2 was negligible in three different-sized blood vessels. The contribution of NO was most prominent in the aorta, whereas that of EDHF was most prominent in the distal mesenteric arteries. The resting membrane potential was significantly deeper and the ACh-induced hyperpolarization was greater in the distal mesenteric arteries than those in the aorta. The expression of eNOS was the highest in the aorta and the lowest in the distal mesenteric arteries. These results indicate that the importance of EDHF increases as the vessel size decreases in endothelium-dependent relaxations in the rat mesenteric circulation.
authors.affiliation: Research Institute of Angiocardiology, Kyushu University, School of Medicine, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: H
authors.initials: H
authors.lastname: Yasutake
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: M K
authors.initials: MK
authors.lastname: Owada
authors.forename: R
authors.initials: R
authors.lastname: Nakaike
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: T
authors.initials: T
authors.lastname: Takayanagi
authors.forename: T
authors.initials: T
authors.lastname: Nagao
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: M
authors.initials: M
authors.lastname: Fujishima
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D001685:Biological Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation
chemical_list: D000959:Antihypertensive Agents; D001685:Biological Factors; D004791:Enzyme Inhibitors; C067410:endothelium-dependent hyperpolarization factor; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester