Kobayashi Shota, Matsumoto Takayuki, Ando Makoto, Iguchi Maika, Taguchi Kumiko, Kobayashi Tsuneo
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University.
Biol Pharm Bull. 2017;40(12):2061-2067. doi: 10.1248/bpb.b17-00210.
Although vasculopathies may occur systemically, there are few reports regarding femoral arteries of type 2 diabetes. Here, we investigated whether contractile response to noradrenaline in femoral arteries would change in type 2 diabetic male Otsuka Long-Evans Tokushima Fatty (OLETF) rat at the chronic stage of disease (1 year old) versus age-matched control Long-Evans Tokushima Otsuka (LETO) rat. OLETF rat exhibited hyperglycemia, hypertension, hyperlipidemia, and hypoinsulinemia compared to age-matched LETO rat. Noradrenaline-induced contraction was increased in femoral arteries in OLETF rats compared with LETO rats whereas serotonin- or phenylephrine-induced contractions were similar between these two animals. Acetylcholine- and sodium nitroprusside-induced relaxations were similar between the two groups. Very small relaxations in femoral arteries induced by clonidine and isoprenaline were obtained in LETO but not OLETF group. Noradrenaline-induced contraction was enhanced by treatment with N-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor, and the between-group difference of contraction was eliminated by such treatment. Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, reduced noradrenaline-induced contraction in both groups, whereas the contraction was greater in OLETF group versus LETO. Femoral arterial protein expression of endothelial NOS, COX-1, and superoxide dismutases were similar between the two groups, whereas reduction of COX-2 expression was seen in OLETF group compared with LETO. Increased contractile responsiveness to noradrenaline is seen in OLETF rat femoral artery and this may be due to reduction of suppressive effect of NO.
尽管血管病变可能全身性发生，但关于2型糖尿病患者股动脉的报道却很少。在此，我们研究了在疾病慢性期（1岁）的2型糖尿病雄性大冢长-艾氏-德岛肥胖（OLETF）大鼠与年龄匹配的对照长-艾氏-德岛大冢（LETO）大鼠相比，股动脉对去甲肾上腺素的收缩反应是否会发生变化。与年龄匹配的LETO大鼠相比，OLETF大鼠表现出高血糖、高血压、高脂血症和低胰岛素血症。与LETO大鼠相比，OLETF大鼠股动脉中去甲肾上腺素诱导的收缩增强，而这两种动物之间5-羟色胺或去氧肾上腺素诱导的收缩相似。两组之间乙酰胆碱和硝普钠诱导的舒张相似。可乐定和异丙肾上腺素在LETO组可诱导股动脉产生非常小的舒张，但在OLETF组未观察到。一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸（L-NNA）处理可增强去甲肾上腺素诱导的收缩，且这种处理消除了两组之间的收缩差异。非选择性环氧化酶（COX）抑制剂吲哚美辛可降低两组中去甲肾上腺素诱导的收缩，而OLETF组的收缩大于LETO组。两组之间内皮型NOS、COX-1和超氧化物歧化酶的股动脉蛋白表达相似，而与LETO组相比，OLETF组COX-2表达降低。在OLETF大鼠股动脉中可见对去甲肾上腺素的收缩反应性增加，这可能是由于一氧化氮抑制作用的减弱。
