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

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Abstract
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+. 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 NG‐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. 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. 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. British Journal of Pharmacology (2000) 130, 549–556; doi:10.1038/sj.bjp.0703354

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