Age-related disappearance of the inhibitory effect of vascular endothelium on agonist-induced vasoconstriction in rat mesenteric vascular beds

Xin Jin, Yukiko Satoh-Otonashi, Yoshito Zamami, Narumi Hobara, Toshihiro Koyama, Pengyuan Sun, Simin Li, Yoshihisa Kitamura, Hiromu Kawasaki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously reported that endothelium-derived hyperpolarizing factor (EDHF)-mediated response time-dependently suppressed methoxamine-induced vasoconstriction in mesenteric vascular beds isolated from 8-week-old rats. We investigated age-related changes in endothelial regulation of methoxamine-induced vasoconstriction. Mesenteric vascular beds isolated from young (8-week-old) to adult (16-week-old) rats were perfused, and changes in perfusion pressure induced by continuous perfusion of methoxamine or high KCl (60 mM) were measured over 180 min. In young preparations with intact endothelium, methoxamine-induced vasoconstriction time-dependently decreased to 20% of the initial levels, while time-dependent reduction was not observed in adult preparations. High KCl-induced vasoconstriction in young and adult preparations did not show time-dependent reduction. Endothelium removal abolished time-dependent reduction of methoxamine-induced vasoconstriction in young preparations and significantly attenuated vasoconstriction in adult preparations. Indomethacin, seratrodast, or tempol but not catalase significantly reduced methoxamine-induced vasoconstriction in adult preparations with endothelium. A23187 (Ca2+-ionophore)-, but not acetylcholine-, induced endothelium-dependent vasodilation in the presence of N G-L-nitro arginine methyl ether in adult preparations was significantly smaller than that in young preparations. These findings suggest that the inhibitory effect of mesenteric vascular endothelium on methoxamine-induced vasoconstriction disappears with aging by reducing EDHF and increasing endothelium-derived contracting factors and reactive oxygen species.

Original languageEnglish
Pages (from-to)372-380
Number of pages9
JournalJournal of Pharmacological Sciences
Volume111
Issue number4
DOIs
Publication statusPublished - 2009

Fingerprint

Methoxamine
Vascular Endothelium
Vasoconstriction
Blood Vessels
Endothelium
seratrodast
Perfusion
Methyl Ethers
Ionophores
Calcimycin
Vasodilation
Indomethacin
Catalase
Reaction Time
Acetylcholine
Arginine
Young Adult
Reactive Oxygen Species
Pressure

Keywords

  • Aging
  • Endothelium-derived contracting factor
  • Endothelium-derived hyperpolarizing factor
  • Methoxamine-induced vasoconstriction
  • Rat mesenteric resistance artery

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Age-related disappearance of the inhibitory effect of vascular endothelium on agonist-induced vasoconstriction in rat mesenteric vascular beds. / Jin, Xin; Satoh-Otonashi, Yukiko; Zamami, Yoshito; Hobara, Narumi; Koyama, Toshihiro; Sun, Pengyuan; Li, Simin; Kitamura, Yoshihisa; Kawasaki, Hiromu.

In: Journal of Pharmacological Sciences, Vol. 111, No. 4, 2009, p. 372-380.

Research output: Contribution to journalArticle

Jin, Xin ; Satoh-Otonashi, Yukiko ; Zamami, Yoshito ; Hobara, Narumi ; Koyama, Toshihiro ; Sun, Pengyuan ; Li, Simin ; Kitamura, Yoshihisa ; Kawasaki, Hiromu. / Age-related disappearance of the inhibitory effect of vascular endothelium on agonist-induced vasoconstriction in rat mesenteric vascular beds. In: Journal of Pharmacological Sciences. 2009 ; Vol. 111, No. 4. pp. 372-380.
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AU - Jin, Xin

AU - Satoh-Otonashi, Yukiko

AU - Zamami, Yoshito

AU - Hobara, Narumi

AU - Koyama, Toshihiro

AU - Sun, Pengyuan

AU - Li, Simin

AU - Kitamura, Yoshihisa

AU - Kawasaki, Hiromu

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N2 - We previously reported that endothelium-derived hyperpolarizing factor (EDHF)-mediated response time-dependently suppressed methoxamine-induced vasoconstriction in mesenteric vascular beds isolated from 8-week-old rats. We investigated age-related changes in endothelial regulation of methoxamine-induced vasoconstriction. Mesenteric vascular beds isolated from young (8-week-old) to adult (16-week-old) rats were perfused, and changes in perfusion pressure induced by continuous perfusion of methoxamine or high KCl (60 mM) were measured over 180 min. In young preparations with intact endothelium, methoxamine-induced vasoconstriction time-dependently decreased to 20% of the initial levels, while time-dependent reduction was not observed in adult preparations. High KCl-induced vasoconstriction in young and adult preparations did not show time-dependent reduction. Endothelium removal abolished time-dependent reduction of methoxamine-induced vasoconstriction in young preparations and significantly attenuated vasoconstriction in adult preparations. Indomethacin, seratrodast, or tempol but not catalase significantly reduced methoxamine-induced vasoconstriction in adult preparations with endothelium. A23187 (Ca2+-ionophore)-, but not acetylcholine-, induced endothelium-dependent vasodilation in the presence of N G-L-nitro arginine methyl ether in adult preparations was significantly smaller than that in young preparations. These findings suggest that the inhibitory effect of mesenteric vascular endothelium on methoxamine-induced vasoconstriction disappears with aging by reducing EDHF and increasing endothelium-derived contracting factors and reactive oxygen species.

AB - We previously reported that endothelium-derived hyperpolarizing factor (EDHF)-mediated response time-dependently suppressed methoxamine-induced vasoconstriction in mesenteric vascular beds isolated from 8-week-old rats. We investigated age-related changes in endothelial regulation of methoxamine-induced vasoconstriction. Mesenteric vascular beds isolated from young (8-week-old) to adult (16-week-old) rats were perfused, and changes in perfusion pressure induced by continuous perfusion of methoxamine or high KCl (60 mM) were measured over 180 min. In young preparations with intact endothelium, methoxamine-induced vasoconstriction time-dependently decreased to 20% of the initial levels, while time-dependent reduction was not observed in adult preparations. High KCl-induced vasoconstriction in young and adult preparations did not show time-dependent reduction. Endothelium removal abolished time-dependent reduction of methoxamine-induced vasoconstriction in young preparations and significantly attenuated vasoconstriction in adult preparations. Indomethacin, seratrodast, or tempol but not catalase significantly reduced methoxamine-induced vasoconstriction in adult preparations with endothelium. A23187 (Ca2+-ionophore)-, but not acetylcholine-, induced endothelium-dependent vasodilation in the presence of N G-L-nitro arginine methyl ether in adult preparations was significantly smaller than that in young preparations. These findings suggest that the inhibitory effect of mesenteric vascular endothelium on methoxamine-induced vasoconstriction disappears with aging by reducing EDHF and increasing endothelium-derived contracting factors and reactive oxygen species.

KW - Aging

KW - Endothelium-derived contracting factor

KW - Endothelium-derived hyperpolarizing factor

KW - Methoxamine-induced vasoconstriction

KW - Rat mesenteric resistance artery

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