title: Crucial roles of nitric oxide synthases in β-adrenoceptor-mediated bladder relaxation in mice.
abstract: The specific roles of nitric oxide (NO) synthases (NOSs) in bladder smooth muscle remain to be elucidated. We examined the roles of NOSs in β-adrenoceptor (AR)-mediated bladder relaxation. Male mice (C57BL6) deficient of neuronal NOS [nNOS-knockout (KO)], endothelial NOS (eNOS-KO), neuronal/endothelial NOS (n/eNOS-KO), neuronal/endothelial/inducible NOS (n/e/iNOS-KO), and their controls [wild-type (WT)] were used. Immunohistochemical analysis was performed in the bladder. Then the responses to relaxing agents and the effects of several inhibitors on the relaxing responses were examined in bladder strips precontracted with carbachol. Immunofluorescence staining showed expressions of nNOS and eNOS in the urothelium and smooth muscle of the bladder. Isoproterenol-induced relaxations were significantly reduced in nNOS-KO mice and were further reduced in n/eNOS-KO and n/e/iNOS-KO mice compared with WT mice. The relaxation in n/e/iNOS-KO mice was almost the same as in n/eNOS-KO mice. Inhibition of Ca2+-activated K+(KCa) channel with charybdotoxin and apamin abolished isoproterenol-induced bladder relaxation in WT mice. Moreover, direct activation of KCachannel with NS1619 caused comparable extent of relaxations among WT, nNOS-KO, and n/eNOS-KO mice. In contrast, NONOate (a NO donor) or hydrogen peroxide (H2O2) (another possible relaxing factor from eNOS) caused minimal relaxations, and catalase (H2O2scavenger) had no inhibitory effects on isoproterenol-induced relaxations. These results indicate that both nNOS and eNOS are substantially involved in β-AR-mediated bladder relaxations in a NO- or H2O2-independent manner through activation of KCachannels.
authors: Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Yohei
authors: Y
authors: Satake
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Kimio
authors: K
authors: Satoh
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Masamichi
authors: M
authors: Nogi
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Junichi
authors: J
authors: Omura
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Shigeo
authors: S
authors: Godo
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Satoshi
authors: S
authors: Miyata
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Hiroki
authors: H
authors: Saito
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Shuhei
authors: S
authors: Tanaka
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Yosuke
authors: Y
authors: Ikumi
authors: Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Shinichi
authors: S
authors: Yamashita
authors: Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yasuhiro
authors: Y
authors: Kaiho
authors: Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors: Masato
authors: M
authors: Tsutsui
authors: Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yoichi
authors: Y
authors: Arai
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and shimo@cardio.med.tohoku.ac.jp.
authors: Hiroaki
authors: H
authors: Shimokawa
mesh_terms: D000818:Animals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012063:Relaxation / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D007545:Isoproterenol
keywords: bladder; nitric oxide; nitric oxide synthase; smooth muscle relaxation