Open AccessDiabetes Mellitus-Induced Enhancement of Prostaglandin F2α-Responses Is Inhibitedby Lipoxygenase- but Not Cyclooxygenase-Inhibitors in Mesenteric Veins and Arteries of Mouse and Rat
Author(s) -
Ikuko Kimura,
Yukiko Hata,
Md. Amirul Islam,
Masayasu Kimura
Publication year - 1994
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.64.65
Subject(s) - nordihydroguaiaretic acid , cyclooxygenase , lipoxygenase , endocrinology , medicine , diabetes mellitus , mesenteric arteries , blood vessel , bradykinin , streptozocin , prostaglandin , eicosanoid , chemistry , streptozotocin , arachidonic acid , artery , enzyme , biochemistry , receptor
The mechanisms responsible for diabetes mellitus-induced enhancement of prostaglandin (PG) F2 alpha 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 PGF2 alpha 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 PGF2 alpha 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 PGF2 alpha 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 PGF2 alpha-induced responses in small blood vessels.