title: Endothelial modulation of agonist-induced vasoconstriction in mesenteric microcirculation.
abstract: It is widely accepted that vascular endothelium regulates vasoconstriction via release of endothelium-derived relaxing factors (EDRF). The mesenteric circulation, which is the largest vascular bed, influences regulation of systemic blood pressure. However, the role of EDRF in the modulation of vascular tone in peripheral mesenteric circulation has not been extensively studied. Therefore, our recent studies investigated the role of the vascular endothelium in the regulation of methoxamine (alpha(1)-adrenoceptor agonist)-induced vasoconstriction and their age-related changes in rat mesenteric vascular beds. In mesenteric vascular beds with intact endothelium isolated from 8 week-old rats, the initial maximum vasoconstriction induced by continuous perfusion of methoxamine was time-dependently decreased during 3 hour-perfusion. Neither nitric oxide synthase inhibitor nor cyclooxygenase inhibitor altered this time-dependent reduction of methoxamine-induced vasoconstriction. Endothelium removal, K(+)-channel inhibitors and gap junction inhibitor significantly inhibited the time-dependent reduction of methoxamine-induced vasoconstriction. In the preparations with intact endothelium from 16 week-old rats, the time-dependent reduction of methoxamine-induced vasoconstriction disappeared. Furthermore, endothelium removal and treatment with cyclooxygenase inhibitor, thromboxane A(2) receptor antagonist or superoxide dismutase mimetic significantly reduced the methoxamine-induced vasoconstriction in the preparations from 16 week-old rats. These findings suggest that vascular endothelium acts to depress methoxamine-induced vasoconstriction by releasing endothelium-derived hyperpolarizing factor (EDHF), and dysfunction in this endothelial modulation develops with ageing.
authors.affiliation: Department of Clinical Pharmaceutical Science, Okayama University, Okayama, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Otonashi-Satoh
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Koyama
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism / Q000502:physiology*; D017629:Gap Junctions / Q000378:metabolism; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D045462:Endothelium-Dependent Relaxing Factors; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D008729:Methoxamine