title: Specific impairment of endothelium-derived hyperpolarizing factor-type relaxation in mesenteric arteries from streptozotocin-induced diabetic mice.
abstract: We hypothesized that the contribution made by endothelium-derived hyperpolarizing factor (EDHF) to acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) might be altered in mesenteric arteries from streptozotocin (STZ)-induced diabetic mice. In endothelium-intact preparations, the ACh-induced EDR (but not the sodium nitroprusside-induced relaxation) was weaker in the STZ group than in age-matched controls. Indomethacin (10 muM) had no significant effect on EDR in either group, indicating that cyclooxygenase products, including prostacyclin, are not involved. This indomethacin-resistant EDR was weaker in the STZ group than in the controls. To isolate the EDHF-resistant component of EDR, charybdotoxin (100 nM) and apamin (100 nM) were present in the bath solution throughout the next experiment. This EDHF-resistant relaxation did not differ significantly between the two groups. On the other hand, the EDHF-mediated relaxation was significantly weaker in the STZ group than in the controls, and it was completely blocked by lysophosphatidylcholine (LPC, 10 microM) in each group. The eNOS protein expression was similar between the two groups. These results suggest that (a) the endothelial dysfunction present in mesenteric arteries from type 1 diabetic mice is largely attributable to reduced EDHF signaling, and (b) LPC may be involved in this attenuation of EDHF-mediated relaxation.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Miyamori
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kamata
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D007213:Indomethacin / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013311:Streptozocin; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D000109:Acetylcholine; D001685:Biological Factors; D017630:Connexins; D004791:Enzyme Inhibitors; D007213:Indomethacin; D008244:Lysophosphatidylcholines; D019335:Nitroarginine; D009599:Nitroprusside; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D013311:Streptozocin; D014665:Vasodilator Agents; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C067410:endothelium-dependent hyperpolarization factor