Diabetes Mellitus-Induced Enhancement of Prostaglandin F2α-Responses Is Inhibited by Lipoxygenase but Not Cyclooxygenase-Inhibitors in Mesenteric Veins and Arteries of Mouse and Rat

The Japanese Journal of Pharmacology

Ikuko Kimura¹  Md. Amirul Islam¹  Yukiko Hata¹  Masayasu Kimura¹ 

[1] Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

关键词: Prostaglandin F2α response;    Diabetic mesenteric vein and artery;    Cyclooxygenase;    Lipoxygenase;    Lipoxygenase inhibitor;   

DOI  :  10.1254/jjp.64.65

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(14)Cited-By(6)The mechanisms responsible for diabetes mellitus-induced enhancement of prostaglandin (PG) F2α response were investigated in vascular smooth muscles isolated from diabetic mice and rats. Streptozocin (150 mg/kg, i.v. bolus, 6 week-elapsed)-ddY mice and (60 mg/kg, i.v. bolus)-Wistar rats and genetically diabetic GK-rats were used. The responses to PGF2α were enhanced in small blood vessels such as mesenteric arteries (diabetic rats) and veins (diabetic mice) and they were reduced in large blood vessels such as the aorta and vena cava (diabetic rats). The enhanced response to PGF2α in diabetic blood vessels was significantly inhibited by nordihydroguaiaretic acid (NDGA) (0.03 mM) and phenidone (0.05 mM), lipoxygenase inhibitors, cycloheximide (1 mg/kg, i.v.), a protein synthesis inhibitor and actinomycin D (2.8 mg/kg, i.v.), a RNA polymerase inhibitor, but neither inhibited by cyclooxygenase inhibitors, a thromboxane antagonist, nor Ca2+ antagonists. The PGF2α response was also enhanced with aging alone, whereas the extent of enhancement was less than that with diabetes mellitus, and not significantly blocked by NDGA. These results demonstrate that diabetes mellitus-induced imbalance in the regulation of the eicosanoid metabolic pathways (suppressed cyclooxygenase and accelerated lipoxygenase) may cause the enhancement of PGF2α-induced responses in small blood vessels.

【 授权许可】

Unknown