Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat

Ayako Makino, Kunihiro Ohuchi, Katsuo Kamata

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Abstract

1. Experiments were designed to investigate the mechanisms underlying the diabetes-related impairment of the vasodilatations of the perfused mesenteric arterial bed induced by acetylcholine (ACh) and K +. 2. In streptozotocin (STZ)-diabetic rats, the ACh-induced endothelium-dependent vasodilatation was attenuated. The dose-response curves for ACh in control and diabetic rats were each shifted to the right by N(G)-nitro-L-arginine (L-NOARG) and by isotonic high K + (60 mM). The ACh dose-response curves under isotonic high K + were not different between control and diabetic rats. 3. We also examined the vasodilatation induced by K +, which is a putative endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vasodilatation induced by a single administration of K + was greatly impaired in STZ-induced diabetic rats. Treatment with charybdotoxin plus apamin abolished the ACh-induced vasodilatation but enhanced the K +-induced response in controls and diabetic rats. After pretreatment with ouabain plus BaCl 2, the ACh-induced vasodilatation was significantly impaired and the K +-induced relaxation was abolished in both control and diabetic rats. 4. The impairment of the endothelium-dependent vasodilatation of the mesenteric arterial bed seen in STZ-induced diabetic rats may be largely due to a defective vascular response to EDHF. It is further suggested that K + is one of the endothelium-derived hyperpolarizing factors and that the vasodilatation response to K + is impaired in the mesenteric arterial bed from diabetic rats.

Original languageEnglish (US)
Pages (from-to)549-556
Number of pages8
JournalBritish Journal of Pharmacology
Volume130
Issue number3
StatePublished - 2000
Externally publishedYes

Fingerprint

Streptozocin
Vasodilation
Endothelium
Acetylcholine
Charybdotoxin
Apamin
Nitroarginine
Ouabain
Blood Vessels
Arginine

Keywords

  • Diabetes
  • Endothelium
  • Endothelium-derived hyperpolarizing factor
  • Mesenteric arterial bed
  • Rat
  • Streptozotocin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat. / Makino, Ayako; Ohuchi, Kunihiro; Kamata, Katsuo.

In: British Journal of Pharmacology, Vol. 130, No. 3, 2000, p. 549-556.

Research output: Contribution to journalArticle

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