PROTEIN-KINASE C-MEDIATED CONTRACTILE RESPONSES OF ARTERIES FROM DIABETIC RATS
PROTEIN-KINASE C-MEDIATED CONTRACTILE RESPONSES OF ARTERIES FROM DIABETIC RATS
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DOI：
10.1111/j.1476-5381.1990.tb12731.x
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发表时间：
1990-10-01
影响因子：
7.3
通讯作者：
MACLEOD, KM
中科院分区：
文献类型：
--
作者：
ABEBE, W;MACLEOD, KM
1 使用 PKC 激活剂佛波醇 12,13-二丁酸酯 (PDB) 和 PKC 抑制剂星形孢菌素研究蛋白激酶 C (PKC) 在介导链脲佐菌素诱导糖尿病 12-14 周雄性大鼠主动脉和肠系膜动脉对去甲肾上腺素 (NA) 增强收缩反应中的作用。 2 糖尿病大鼠的主动脉和肠系膜动脉对 NA 的最大收缩反应与年龄匹配的对照动物的动脉反应相比显着增强。最大 NA 响应增加了 59.6 .+-。主动脉 7.9%，54.9 .+-。与各自的对照组相比，糖尿病动物的肠系膜动脉为 7.4%。图3用十字孢菌素(5×10-8M)预处理对照动物和糖尿病动物的主动脉和肠系膜动脉，导致对最大浓度NA(主动脉中10-5M；肠系膜动脉中3×10-5M)的收缩反应的显着抑制。在星形孢菌素存在的情况下，对照组和糖尿病大鼠的动脉收缩反应强度没有观察到差异。 4.与对照动物的动脉反应相比，糖尿病大鼠的肠系膜动脉对PDB的最大收缩反应显着增加(增加45.0±4.9％)。相比之下，对照组和糖尿病大鼠的动脉收缩反应对 PDB 的反应程度没有观察到显着差异。 5星形孢菌素(5×10-8M)导致对照大鼠和糖尿病大鼠的动脉收缩反应显着减弱至最大浓度的PDB(3×10-6M)。在星形孢菌素存在的情况下，对照大鼠和糖尿病大鼠的肠系膜动脉对 PDB 的收缩反应程度的差异被消除。 6 在不存在细胞外 Ca2+ 且存在 Ca2+ 通道阻滞剂、硝苯地平 (3×10-6M) 或维拉帕米 (3×10-6M) 的情况下，对照大鼠和糖尿病大鼠的主动脉和肠系膜动脉对 PDB 的收缩反应降低。在这些条件下，对照组和糖尿病大鼠的肠系膜动脉对 PDB 的收缩反应程度没有差异。 7 这些数据表明，链脲佐菌素诱导的糖尿病大鼠的主动脉和肠系膜动脉对 NA 的收缩反应增强，可能至少部分是由于 PKC 激活增加所致。此外，PKC 介导过程的激活增加（依赖于细胞外 Ca2+ 的存在）可能进一步有助于增强糖尿病肠系膜动脉对 NA 的收缩反应。
1 The role of protein kinase C (PKC) in mediating enhanced contractile responses of aortae and mesenteric arteries from male rats with 12-14 week streptozotocin-induced diabetes to noradrenaline (NA) was investigated using the PKC activator, phorbol 12,13-dibutyrate (PDB), and the PKC inhibitor, staurosporine. 2 Maximum contractile responses of aortae and mesenteric arteries from diabetic rats to NA were significantly enhanced with responses of arteries from age-matched control animals. The maximum NA responses were increased by 59.6 .+-. 7.9% in aortae and by 54.9 .+-. 7.4% in mesenteric arteries from diabetic animals, compared to their respective controls. 3 Pretreatment of aortae and mesenteric arteries from both control and diabetic animals with staurosporine (5 .times. 10-8 M) caused marked inhibition of contractile responses to a maximum concentration of NA (10-5 M in aortae; 3 .times. 10-5 M in mesenteric arteries). In the presence of staurosporine, no difference was observed in the magnitude of contractile responses of arteries from control and diabetic rats to NA. 4. Maximum contractile responses of mesenteric arteries from diabetic rats to PDB were significantly increased (by 45.0 .+-. 4.9%) compared to responses of arteries from control animals. In contrast, no significant difference was observed in the magnitude of contractile responses of arteries from control and diabetic rats to PDB. 5 Staurosporine (5 .times. 10-8 M) caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 .times. 10-6 M). In the presence of staurosporine, the difference in magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB was abolished. 6 Contractile responses of aortae and mesenteric arteries from control and diabetic rats to PDB were reduced in the absence of extracellular Ca2+, and in the presence of the Ca2+ channel blockers, nifedipine (3 .times. 10-6 M) or verapamil (3 .times. 10-6 M). Under these conditions, no difference was found in the magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB. 7 These data suggest that enhanced contractile responses of aortae and mesenteric arteries from streptozotocin-induced diabetic rats to NA may result, at least in part, from increased activation of PKC. In addition, increased activation of PKC-mediated processes, which are dependent on the presence of extracellular Ca2+, may further contribute to the enhanced contractile responses of diabetic mesenteric arteries to NA.