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

Research output: Contribution to journalArticle

84 Scopus citations

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 BaCl2, 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
DOIs
StatePublished - 2000

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat'. Together they form a unique fingerprint.

  • Cite this