Inhibitory effect of valves on endothelium-dependent relaxations to calcium ionophore in canine saphenous vein

Daihiko Eguchi, Zvonimir S Katusic

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3 Citations (Scopus)

Abstract

The present study was designed to evaluate endothelium-dependent relaxation to the calcium ionophore A-23187 in isolated canine saphenous veins. Isometric force recordings and cGMP measurements using isolated veins with and without valves were performed. During contractions to U-46619 (3 × 10 -7 M), endothelium-dependent relaxations to A-23187 (10 -9-10 -6 M) were significantly reduced in rings with valves compared with rings without valves. Endothelial removal abolished A-23187-induced relaxation. Relaxations to forskolin (FK; 10 -8-10 -5 M) and diethylaminodiazen-1-ium-1,2-dionate; DEA-NONOate, 10 -9-10 -5 M) were identical in rings with and without valves. In rings without valves, a nitric oxide synthase inhibitor, N G-nitro-L-arginine methyl ester (L-NAME; 3 × 10 -4 M), and a cyclooxygenase inhibitor, indomethacin (10 -5 M), partially reduced A-23187-induced relaxation. However, in rings with valves, L-NAME had no effect, whereas indomethacin abolished the relaxation to A-23187. A selective soluble guanylate cyclase inhibitor, 1H-[1,2,4]-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 3× 10 -6 M), had no effect on the relaxation to A-23187 in either group. In contrast, ODQ abolished the A-23187-induced increase in cGMP levels, suggesting that relaxation to nitric oxide released by A-23187 is independent of increases in cGMP. These results demonstrate that endothelium-dependent relaxation to A-23187 is reduced in regions of veins with valves compared with relaxation in the nonvalvular venous wall. Lower production of nitric oxide in endothelial cells of valvular segments appears to be a mechanism responsible for reduced reactivity to A-23187.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
StatePublished - Feb 2001

Fingerprint

Calcium Ionophores
Saphenous Vein
Calcimycin
Endothelium
Canidae
NG-Nitroarginine Methyl Ester
Indomethacin
Veins
Nitric Oxide
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Cyclooxygenase Inhibitors
Colforsin
Nitric Oxide Synthase
Endothelial Cells

Keywords

  • 1H-[1,2,4]-oxadiazolo-[4,3-a]quinoxalin-1-one
  • Graft failure
  • Guanosine cyclic 5′-monophosphate
  • Indomethacin
  • N -nitro-L-arginine methyl ester
  • Venous valve

ASJC Scopus subject areas

  • Physiology

Cite this

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title = "Inhibitory effect of valves on endothelium-dependent relaxations to calcium ionophore in canine saphenous vein",
abstract = "The present study was designed to evaluate endothelium-dependent relaxation to the calcium ionophore A-23187 in isolated canine saphenous veins. Isometric force recordings and cGMP measurements using isolated veins with and without valves were performed. During contractions to U-46619 (3 × 10 -7 M), endothelium-dependent relaxations to A-23187 (10 -9-10 -6 M) were significantly reduced in rings with valves compared with rings without valves. Endothelial removal abolished A-23187-induced relaxation. Relaxations to forskolin (FK; 10 -8-10 -5 M) and diethylaminodiazen-1-ium-1,2-dionate; DEA-NONOate, 10 -9-10 -5 M) were identical in rings with and without valves. In rings without valves, a nitric oxide synthase inhibitor, N G-nitro-L-arginine methyl ester (L-NAME; 3 × 10 -4 M), and a cyclooxygenase inhibitor, indomethacin (10 -5 M), partially reduced A-23187-induced relaxation. However, in rings with valves, L-NAME had no effect, whereas indomethacin abolished the relaxation to A-23187. A selective soluble guanylate cyclase inhibitor, 1H-[1,2,4]-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 3× 10 -6 M), had no effect on the relaxation to A-23187 in either group. In contrast, ODQ abolished the A-23187-induced increase in cGMP levels, suggesting that relaxation to nitric oxide released by A-23187 is independent of increases in cGMP. These results demonstrate that endothelium-dependent relaxation to A-23187 is reduced in regions of veins with valves compared with relaxation in the nonvalvular venous wall. Lower production of nitric oxide in endothelial cells of valvular segments appears to be a mechanism responsible for reduced reactivity to A-23187.",
keywords = "1H-[1,2,4]-oxadiazolo-[4,3-a]quinoxalin-1-one, Graft failure, Guanosine cyclic 5′-monophosphate, Indomethacin, N -nitro-L-arginine methyl ester, Venous valve",
author = "Daihiko Eguchi and Katusic, {Zvonimir S}",
year = "2001",
month = "2",
language = "English (US)",
volume = "280",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
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T1 - Inhibitory effect of valves on endothelium-dependent relaxations to calcium ionophore in canine saphenous vein

AU - Eguchi, Daihiko

AU - Katusic, Zvonimir S

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Y1 - 2001/2

N2 - The present study was designed to evaluate endothelium-dependent relaxation to the calcium ionophore A-23187 in isolated canine saphenous veins. Isometric force recordings and cGMP measurements using isolated veins with and without valves were performed. During contractions to U-46619 (3 × 10 -7 M), endothelium-dependent relaxations to A-23187 (10 -9-10 -6 M) were significantly reduced in rings with valves compared with rings without valves. Endothelial removal abolished A-23187-induced relaxation. Relaxations to forskolin (FK; 10 -8-10 -5 M) and diethylaminodiazen-1-ium-1,2-dionate; DEA-NONOate, 10 -9-10 -5 M) were identical in rings with and without valves. In rings without valves, a nitric oxide synthase inhibitor, N G-nitro-L-arginine methyl ester (L-NAME; 3 × 10 -4 M), and a cyclooxygenase inhibitor, indomethacin (10 -5 M), partially reduced A-23187-induced relaxation. However, in rings with valves, L-NAME had no effect, whereas indomethacin abolished the relaxation to A-23187. A selective soluble guanylate cyclase inhibitor, 1H-[1,2,4]-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 3× 10 -6 M), had no effect on the relaxation to A-23187 in either group. In contrast, ODQ abolished the A-23187-induced increase in cGMP levels, suggesting that relaxation to nitric oxide released by A-23187 is independent of increases in cGMP. These results demonstrate that endothelium-dependent relaxation to A-23187 is reduced in regions of veins with valves compared with relaxation in the nonvalvular venous wall. Lower production of nitric oxide in endothelial cells of valvular segments appears to be a mechanism responsible for reduced reactivity to A-23187.

AB - The present study was designed to evaluate endothelium-dependent relaxation to the calcium ionophore A-23187 in isolated canine saphenous veins. Isometric force recordings and cGMP measurements using isolated veins with and without valves were performed. During contractions to U-46619 (3 × 10 -7 M), endothelium-dependent relaxations to A-23187 (10 -9-10 -6 M) were significantly reduced in rings with valves compared with rings without valves. Endothelial removal abolished A-23187-induced relaxation. Relaxations to forskolin (FK; 10 -8-10 -5 M) and diethylaminodiazen-1-ium-1,2-dionate; DEA-NONOate, 10 -9-10 -5 M) were identical in rings with and without valves. In rings without valves, a nitric oxide synthase inhibitor, N G-nitro-L-arginine methyl ester (L-NAME; 3 × 10 -4 M), and a cyclooxygenase inhibitor, indomethacin (10 -5 M), partially reduced A-23187-induced relaxation. However, in rings with valves, L-NAME had no effect, whereas indomethacin abolished the relaxation to A-23187. A selective soluble guanylate cyclase inhibitor, 1H-[1,2,4]-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 3× 10 -6 M), had no effect on the relaxation to A-23187 in either group. In contrast, ODQ abolished the A-23187-induced increase in cGMP levels, suggesting that relaxation to nitric oxide released by A-23187 is independent of increases in cGMP. These results demonstrate that endothelium-dependent relaxation to A-23187 is reduced in regions of veins with valves compared with relaxation in the nonvalvular venous wall. Lower production of nitric oxide in endothelial cells of valvular segments appears to be a mechanism responsible for reduced reactivity to A-23187.

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KW - Indomethacin

KW - N -nitro-L-arginine methyl ester

KW - Venous valve

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