Role of Endogenous Nitric Oxide Generation in the Regulation of Vascular Tone and Reactivity in Small Vessels as Investigated in Transgenic Mice Using Synchrotron Radiation Microangiography

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role in regulation of vascular tone and reactivity. The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system usin...

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Veröffentlicht in:Nitric oxide 2001-10, Vol.5 (5), p.494-503
Hauptverfasser: Yamashita, Tomoya, Kawashima, Seinosuke, Ozaki, Masanori, Namiki, Masayuki, Satomi-Kobayashi, Seimi, Seno, Tadashi, Matsuda, Yasuaki, Inoue, Nobutaka, Hirata, Ken-ichi, Akita, Hozuka, Umetani, Keiji, Tanaka, Etsuro, Mori, Hidezo, Yokoyama, Mitsuhiro
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container_end_page 503
container_issue 5
container_start_page 494
container_title Nitric oxide
container_volume 5
creator Yamashita, Tomoya
Kawashima, Seinosuke
Ozaki, Masanori
Namiki, Masayuki
Satomi-Kobayashi, Seimi
Seno, Tadashi
Matsuda, Yasuaki
Inoue, Nobutaka
Hirata, Ken-ichi
Akita, Hozuka
Umetani, Keiji
Tanaka, Etsuro
Mori, Hidezo
Yokoyama, Mitsuhiro
description Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role in regulation of vascular tone and reactivity. The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system using monochromatic synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic contrast media was injected, and microangiography was performed in hindlimbs of mice. Serial images of the small blood vessels (diameter
doi_str_mv 10.1006/niox.2001.0376
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The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system using monochromatic synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic contrast media was injected, and microangiography was performed in hindlimbs of mice. Serial images of the small blood vessels (diameter &lt;200 μm) were recorded by the SR microangiography system. At basal conditions, the diameter of tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 ± 8 versus 132 ± 8 μm; P &lt; 0.01). l-NAME treatment decreased the vessel diameter and canceled the difference in vessel diameters between two genotypes. Acetylcholine- and sodium nitroprusside-induced relaxations of small vessels were significantly reduced in Tg mice compared with wild-type mice (35.0 ± 9.4 versus 61.6 ± 6.7%, 85.0 ± 10.2 versus 97.3 ± 6.7% of the maximum relaxation, respectively). Our data provide the evidence that overproduced NO from endothelium reduces vascular tone and plays a pivotal role in regulation of vascular tone in small vessels. Furthermore, the reduced NO-mediated relaxation in small vessels of eNOS-Tg mice is demonstrated for the first time in vivo. 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Kawashima, Seinosuke ; Ozaki, Masanori ; Namiki, Masayuki ; Satomi-Kobayashi, Seimi ; Seno, Tadashi ; Matsuda, Yasuaki ; Inoue, Nobutaka ; Hirata, Ken-ichi ; Akita, Hozuka ; Umetani, Keiji ; Tanaka, Etsuro ; Mori, Hidezo ; Yokoyama, Mitsuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-4a345e9ce6fcb211f249dbff5ef6c96b6a405130e3e65b7fe13e0b581a030ec43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Angiography - methods</topic><topic>Animals</topic><topic>Cattle</topic><topic>endothelial nitric oxide synthase</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Hindlimb - blood supply</topic><topic>Hindlimb - diagnostic imaging</topic><topic>In Vitro Techniques</topic><topic>Lipopolysaccharides - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>microangiography</topic><topic>microvascular reactivity</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle Contraction - physiology</topic><topic>Muscle Relaxation - drug effects</topic><topic>Muscle Relaxation - physiology</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Neovascularization, Physiologic</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>nitric oxide</topic><topic>Nitric Oxide - physiology</topic><topic>Nitric Oxide Synthase - physiology</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Nitric Oxide Synthase Type III</topic><topic>Nitroprusside - pharmacology</topic><topic>Papaverine - pharmacology</topic><topic>synchrotron radiation</topic><topic>Synchrotrons - instrumentation</topic><topic>transgenic mouse</topic><topic>vascular tone</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamashita, Tomoya</creatorcontrib><creatorcontrib>Kawashima, Seinosuke</creatorcontrib><creatorcontrib>Ozaki, Masanori</creatorcontrib><creatorcontrib>Namiki, Masayuki</creatorcontrib><creatorcontrib>Satomi-Kobayashi, Seimi</creatorcontrib><creatorcontrib>Seno, Tadashi</creatorcontrib><creatorcontrib>Matsuda, Yasuaki</creatorcontrib><creatorcontrib>Inoue, Nobutaka</creatorcontrib><creatorcontrib>Hirata, Ken-ichi</creatorcontrib><creatorcontrib>Akita, Hozuka</creatorcontrib><creatorcontrib>Umetani, Keiji</creatorcontrib><creatorcontrib>Tanaka, Etsuro</creatorcontrib><creatorcontrib>Mori, Hidezo</creatorcontrib><creatorcontrib>Yokoyama, Mitsuhiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nitric oxide</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamashita, Tomoya</au><au>Kawashima, Seinosuke</au><au>Ozaki, Masanori</au><au>Namiki, Masayuki</au><au>Satomi-Kobayashi, Seimi</au><au>Seno, Tadashi</au><au>Matsuda, Yasuaki</au><au>Inoue, Nobutaka</au><au>Hirata, Ken-ichi</au><au>Akita, Hozuka</au><au>Umetani, Keiji</au><au>Tanaka, Etsuro</au><au>Mori, Hidezo</au><au>Yokoyama, Mitsuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Endogenous Nitric Oxide Generation in the Regulation of Vascular Tone and Reactivity in Small Vessels as Investigated in Transgenic Mice Using Synchrotron Radiation Microangiography</atitle><jtitle>Nitric oxide</jtitle><addtitle>Nitric Oxide</addtitle><date>2001-10-01</date><risdate>2001</risdate><volume>5</volume><issue>5</issue><spage>494</spage><epage>503</epage><pages>494-503</pages><issn>1089-8603</issn><eissn>1089-8611</eissn><abstract>Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role in regulation of vascular tone and reactivity. The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system using monochromatic synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic contrast media was injected, and microangiography was performed in hindlimbs of mice. Serial images of the small blood vessels (diameter &lt;200 μm) were recorded by the SR microangiography system. At basal conditions, the diameter of tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 ± 8 versus 132 ± 8 μm; P &lt; 0.01). l-NAME treatment decreased the vessel diameter and canceled the difference in vessel diameters between two genotypes. Acetylcholine- and sodium nitroprusside-induced relaxations of small vessels were significantly reduced in Tg mice compared with wild-type mice (35.0 ± 9.4 versus 61.6 ± 6.7%, 85.0 ± 10.2 versus 97.3 ± 6.7% of the maximum relaxation, respectively). Our data provide the evidence that overproduced NO from endothelium reduces vascular tone and plays a pivotal role in regulation of vascular tone in small vessels. Furthermore, the reduced NO-mediated relaxation in small vessels of eNOS-Tg mice is demonstrated for the first time in vivo. SR microangiography allows us to evaluate the reactivity in small-sized vessels and appears to be a powerful tool for assessing the microvascular circulation in vivo.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11587564</pmid><doi>10.1006/niox.2001.0376</doi><tpages>10</tpages></addata></record>
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subjects Angiography - methods
Animals
Cattle
endothelial nitric oxide synthase
Enzyme Inhibitors - pharmacology
Hindlimb - blood supply
Hindlimb - diagnostic imaging
In Vitro Techniques
Lipopolysaccharides - metabolism
Mice
Mice, Transgenic
microangiography
microvascular reactivity
Muscle Contraction - drug effects
Muscle Contraction - physiology
Muscle Relaxation - drug effects
Muscle Relaxation - physiology
Muscle, Smooth, Vascular - physiology
Neovascularization, Physiologic
NG-Nitroarginine Methyl Ester - pharmacology
nitric oxide
Nitric Oxide - physiology
Nitric Oxide Synthase - physiology
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Nitroprusside - pharmacology
Papaverine - pharmacology
synchrotron radiation
Synchrotrons - instrumentation
transgenic mouse
vascular tone
Vasodilation - drug effects
Vasodilator Agents - pharmacology
title Role of Endogenous Nitric Oxide Generation in the Regulation of Vascular Tone and Reactivity in Small Vessels as Investigated in Transgenic Mice Using Synchrotron Radiation Microangiography
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