Mori Asami, Suzawa Hironori, Sakamoto Kenji, Nakahara Tsutomu, Ishii Kunio
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences.
Biol Pharm Bull. 2015;38(10):1536-41. doi: 10.1248/bpb.b15-00303.
The aim of this study was to examine the effects of elcatonin, a synthetic derivative of eel calcitonin, on rat retinal blood vessels, and to determine how diabetes affects the retinal vascular responses. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal blood vessels contained in the digital images. Both systemic blood pressure and heart rate were continuously recorded. Elcatonin increased the diameter of retinal blood vessels but decreased mean blood pressure in a dose-dependent manner, whereas it had no significant effect on heart rate. A diminished retinal vasodilator response and significant pressor response to elcatonin were observed in rats injected intravenously with N(G)-nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor. Intravitreal injection of indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ22536, an adenylyl cyclase inhibitor, markedly attenuated the vasodilator effects of elcatonin on retinal blood vessels. The retinal vasodilator responses to elcatonin were unaffected 2 weeks after the induction of diabetes by a combination of streptozotocin treatment and D-glucose feeding. These results suggest that elcatonin dilates rat retinal blood vessels via NO- and COX-dependent mechanisms and that the adenylyl cyclase-adenosine 3',5'-cyclic monophosphate system plays a major role in the vasodilator mechanisms. The retinal vasodilatory effects of elcatonin seem to be preserved at early stages of diabetes.
本研究旨在探讨鳗鱼降钙素的合成衍生物依降钙素对大鼠视网膜血管的影响，并确定糖尿病如何影响视网膜血管反应。使用原装高分辨率数字眼底相机在体内采集眼底图像。通过测量数字图像中包含的视网膜血管直径来评估视网膜血管反应。连续记录全身血压和心率。依降钙素以剂量依赖性方式增加视网膜血管直径，但降低平均血压，而对心率无显著影响。在静脉注射一氧化氮（NO）合酶抑制剂N(G)-硝基-L-精氨酸甲酯的大鼠中，观察到依降钙素的视网膜血管舒张反应减弱和显著的升压反应。玻璃体内注射非选择性环氧化酶（COX）抑制剂吲哚美辛和腺苷酸环化酶抑制剂SQ22536，可显著减弱依降钙素对视网膜血管的舒张作用。链脲佐菌素治疗和D-葡萄糖喂养联合诱导糖尿病2周后，依降钙素的视网膜血管舒张反应未受影响。这些结果表明，依降钙素通过NO和COX依赖性机制扩张大鼠视网膜血管，腺苷酸环化酶-腺苷3',5'-环磷酸系统在血管舒张机制中起主要作用。依降钙素的视网膜血管舒张作用在糖尿病早期似乎得以保留。
