New molecular mechanisms for cardiovascular disease

Contribution of endothelium-derived hyperpolarizing factor in the regulation of vasoconstriction in peripheral resistance arteries

Xin Jin, Yukiko Satoh-Otonashi, Yoshito Zamami, Shingo Takatori, Narumi Hashikawa-Hobara, Yoshihisa Kitamura, Hiromu Kawasaki

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Endothelium regulates vascular tone via release of endothelium-derived relaxing factors (EDRF) including nitric oxide (NO), prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vascular bed produces vascular resistance to develop blood pressure and regulate tissue blood flow that plays an important role in maintenance of systemic blood pressure. There is now strong evidence that in these small resistance arteries, EDHF plays a major role in the response to vasoactive substances and regulation of vascular tone. Pharmacological analysis to investigate the role of the vascular endothelium in the regulation of α 1-adrenoceptor agonist (methoxamine)-induced vasoconstriction in rat mesenteric vascular beds showed that vasoconstriction induced by continuous perfusion of methoxamine (7 μM), but not high KCl (60 mM), time-dependently decreased to 20% of the initial constriction. The time-dependent reduction of methoxamine-induced vasoconstriction was inhibited by endothelium removal, inhibitor of EDHF (30 mM KCl, K +-channel blockers), and gap-junction inhibitor, but not NO synthase inhibitor and cyclooxygenase inhibitor and ageing. These results suggest that vascular endothelium counteracts to normalize excess vasoconstriction of the mesenteric resistance arteries by releasing EDHF, which is associated with activation of multiple K +-channels and gap junction involvement and markedly decreases with ageing.

Original languageEnglish
Pages (from-to)332-336
Number of pages5
JournalJournal of Pharmacological Sciences
Volume116
Issue number4
DOIs
Publication statusPublished - 2011

Fingerprint

Vasoconstriction
Vascular Resistance
Endothelium
Methoxamine
Cardiovascular Diseases
Arteries
Vascular Endothelium
Blood Vessels
Gap Junctions
Blood Pressure
Endothelium-Dependent Relaxing Factors
Mesenteric Arteries
Cyclooxygenase Inhibitors
Epoprostenol
Constriction
Nitric Oxide Synthase
Adrenergic Receptors
Nitric Oxide
Perfusion
Maintenance

Keywords

  • Age
  • Cardiovascular disease
  • Endothelial regulation of vasoconstriction
  • Endothelium-derived hyperpolarizing factor
  • Rat mesenteric artery

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

New molecular mechanisms for cardiovascular disease : Contribution of endothelium-derived hyperpolarizing factor in the regulation of vasoconstriction in peripheral resistance arteries. / Jin, Xin; Satoh-Otonashi, Yukiko; Zamami, Yoshito; Takatori, Shingo; Hashikawa-Hobara, Narumi; Kitamura, Yoshihisa; Kawasaki, Hiromu.

In: Journal of Pharmacological Sciences, Vol. 116, No. 4, 2011, p. 332-336.

Research output: Contribution to journalArticle

Jin, Xin ; Satoh-Otonashi, Yukiko ; Zamami, Yoshito ; Takatori, Shingo ; Hashikawa-Hobara, Narumi ; Kitamura, Yoshihisa ; Kawasaki, Hiromu. / New molecular mechanisms for cardiovascular disease : Contribution of endothelium-derived hyperpolarizing factor in the regulation of vasoconstriction in peripheral resistance arteries. In: Journal of Pharmacological Sciences. 2011 ; Vol. 116, No. 4. pp. 332-336.
@article{c1c10fef2e124de7ad1f345eabbb8251,
title = "New molecular mechanisms for cardiovascular disease: Contribution of endothelium-derived hyperpolarizing factor in the regulation of vasoconstriction in peripheral resistance arteries",
abstract = "Endothelium regulates vascular tone via release of endothelium-derived relaxing factors (EDRF) including nitric oxide (NO), prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vascular bed produces vascular resistance to develop blood pressure and regulate tissue blood flow that plays an important role in maintenance of systemic blood pressure. There is now strong evidence that in these small resistance arteries, EDHF plays a major role in the response to vasoactive substances and regulation of vascular tone. Pharmacological analysis to investigate the role of the vascular endothelium in the regulation of α 1-adrenoceptor agonist (methoxamine)-induced vasoconstriction in rat mesenteric vascular beds showed that vasoconstriction induced by continuous perfusion of methoxamine (7 μM), but not high KCl (60 mM), time-dependently decreased to 20{\%} of the initial constriction. The time-dependent reduction of methoxamine-induced vasoconstriction was inhibited by endothelium removal, inhibitor of EDHF (30 mM KCl, K +-channel blockers), and gap-junction inhibitor, but not NO synthase inhibitor and cyclooxygenase inhibitor and ageing. These results suggest that vascular endothelium counteracts to normalize excess vasoconstriction of the mesenteric resistance arteries by releasing EDHF, which is associated with activation of multiple K +-channels and gap junction involvement and markedly decreases with ageing.",
keywords = "Age, Cardiovascular disease, Endothelial regulation of vasoconstriction, Endothelium-derived hyperpolarizing factor, Rat mesenteric artery",
author = "Xin Jin and Yukiko Satoh-Otonashi and Yoshito Zamami and Shingo Takatori and Narumi Hashikawa-Hobara and Yoshihisa Kitamura and Hiromu Kawasaki",
year = "2011",
doi = "10.1254/jphs.10R30FM",
language = "English",
volume = "116",
pages = "332--336",
journal = "Journal of Pharmacological Sciences",
issn = "1347-8648",
publisher = "The Japanese Pharmacological Society",
number = "4",

}

TY - JOUR

T1 - New molecular mechanisms for cardiovascular disease

T2 - Contribution of endothelium-derived hyperpolarizing factor in the regulation of vasoconstriction in peripheral resistance arteries

AU - Jin, Xin

AU - Satoh-Otonashi, Yukiko

AU - Zamami, Yoshito

AU - Takatori, Shingo

AU - Hashikawa-Hobara, Narumi

AU - Kitamura, Yoshihisa

AU - Kawasaki, Hiromu

PY - 2011

Y1 - 2011

N2 - Endothelium regulates vascular tone via release of endothelium-derived relaxing factors (EDRF) including nitric oxide (NO), prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vascular bed produces vascular resistance to develop blood pressure and regulate tissue blood flow that plays an important role in maintenance of systemic blood pressure. There is now strong evidence that in these small resistance arteries, EDHF plays a major role in the response to vasoactive substances and regulation of vascular tone. Pharmacological analysis to investigate the role of the vascular endothelium in the regulation of α 1-adrenoceptor agonist (methoxamine)-induced vasoconstriction in rat mesenteric vascular beds showed that vasoconstriction induced by continuous perfusion of methoxamine (7 μM), but not high KCl (60 mM), time-dependently decreased to 20% of the initial constriction. The time-dependent reduction of methoxamine-induced vasoconstriction was inhibited by endothelium removal, inhibitor of EDHF (30 mM KCl, K +-channel blockers), and gap-junction inhibitor, but not NO synthase inhibitor and cyclooxygenase inhibitor and ageing. These results suggest that vascular endothelium counteracts to normalize excess vasoconstriction of the mesenteric resistance arteries by releasing EDHF, which is associated with activation of multiple K +-channels and gap junction involvement and markedly decreases with ageing.

AB - Endothelium regulates vascular tone via release of endothelium-derived relaxing factors (EDRF) including nitric oxide (NO), prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vascular bed produces vascular resistance to develop blood pressure and regulate tissue blood flow that plays an important role in maintenance of systemic blood pressure. There is now strong evidence that in these small resistance arteries, EDHF plays a major role in the response to vasoactive substances and regulation of vascular tone. Pharmacological analysis to investigate the role of the vascular endothelium in the regulation of α 1-adrenoceptor agonist (methoxamine)-induced vasoconstriction in rat mesenteric vascular beds showed that vasoconstriction induced by continuous perfusion of methoxamine (7 μM), but not high KCl (60 mM), time-dependently decreased to 20% of the initial constriction. The time-dependent reduction of methoxamine-induced vasoconstriction was inhibited by endothelium removal, inhibitor of EDHF (30 mM KCl, K +-channel blockers), and gap-junction inhibitor, but not NO synthase inhibitor and cyclooxygenase inhibitor and ageing. These results suggest that vascular endothelium counteracts to normalize excess vasoconstriction of the mesenteric resistance arteries by releasing EDHF, which is associated with activation of multiple K +-channels and gap junction involvement and markedly decreases with ageing.

KW - Age

KW - Cardiovascular disease

KW - Endothelial regulation of vasoconstriction

KW - Endothelium-derived hyperpolarizing factor

KW - Rat mesenteric artery

UR - http://www.scopus.com/inward/record.url?scp=84860390575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860390575&partnerID=8YFLogxK

U2 - 10.1254/jphs.10R30FM

DO - 10.1254/jphs.10R30FM

M3 - Article

VL - 116

SP - 332

EP - 336

JO - Journal of Pharmacological Sciences

JF - Journal of Pharmacological Sciences

SN - 1347-8648

IS - 4

ER -