Altered endothelium-dependent and -independent hyperpolarization and endothelium-dependent relaxation in carotid arteries isolated from streptozotocin-induced diabetic rats.
We examined endothelium-dependent and -independent hyperpolarizations and endothelium-dependent relaxation responses in carotid arteries isolated from streptozotocin-induced diabetic rats and age-matched controls. The resting membrane potentials were not significantly different between control and diabetic carotid arteries. The endothelium-dependent hyperpolarization induced by acetylcholine, which was inhibited by TEA but not by glibenclamide or by treatment with either a high concentration of glucose or pertussis toxin, was significantly weaker in diabetic arteries than in the controls. The relaxation responses to acetylcholine in carotid artery rings were significantly decreased in streptozotocin-diabetic rats. Treatment with NG-nitro-L-arginine (L-NOARG) inhibited the acetylcholine-induced maximal relaxation by 80% and 30% in control and streptozotocin-diabetic rats, respectively, and the simultaneous application of L-NOARG and indomethacin had a more potent inhibitory effect on this relaxation in both groups. The release of 6-keto-prostaglandin F1alpha and that of thromboxane A2 in response to methoxamine or methoxamine plus acetylcholine were both markedly decreased in diabetic rats. The cromakalim-induced hyperpolarization of the carotid artery, which was completely prevented by glibenclamide, was also significantly weaker in diabetic arteries than in the controls. These results suggest that changes in (1) various K+ channels on smooth muscle, (2) the biosynthesis of cyclooxygenase products and (3) endothelium-dependent relaxation may be important factors in the development of diabetic complications in the carotid artery.
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. kamata@hoshi.ac.jp
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D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D019806:Cromakalim / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D019806:Cromakalim; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D037342:Pertussis Toxin; D000109:Acetylcholine