Kaito N, Onoue H, Abe T
Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan.
Peptides. 1995;16(6):1127-32. doi: 10.1016/0196-9781(95)00079-y.
We investigated the effect of endothelin-1 on relaxation responses induced by vasodilator substances in canine middle cerebral arteries to better understand regulation of cerebrovascular tone and its potential impact on mechanism of cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in helical strips of canine cerebral arteries (EC50; 4.62 x 10(-9) M). Pretreatment with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation elicited by substance P and endothelium-independent relaxations by nitroglycerin, prostaglandin I2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-independent relaxations, it did inhibit endothelium-dependent relaxation caused by substance P. A low concentration (10(-10) M) of endothelin-1 also significantly reduced endothelium-dependent relaxation of canine mesenteric arteries induced by acetylcholine. Other vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit endothelium-dependent and -independent relaxations. These results indicate that endothelin-1 not only produces cerebral vasoconstriction but also interferes with vasodilator mechanisms and that endothelium-dependent vasodilation is more sensitive to the inhibitory effect of endothelin-1 than endothelium-independent vasodiltion.
我们研究了内皮素 -1 对犬大脑中动脉血管舒张物质诱导的舒张反应的影响，以更好地理解脑血管张力的调节及其对脑血管痉挛机制的潜在影响。内皮素 -1 在犬脑动脉螺旋条带中引起浓度依赖性收缩（半数有效浓度；4.62×10⁻⁹ M）。用 10⁻⁹ M 内皮素 -1 预处理可显著降低 P 物质引起的内皮依赖性舒张以及硝酸甘油、前列腺素 I2 和氯化钾引起的非内皮依赖性舒张。虽然较低浓度（10⁻¹⁰ M）的内皮素 -1 不影响这些非内皮依赖性舒张，但它确实抑制了 P 物质引起的内皮依赖性舒张。低浓度（10⁻¹⁰ M）的内皮素 -1 也显著降低了乙酰胆碱诱导的犬肠系膜动脉的内皮依赖性舒张。其他血管收缩肽如血管紧张素 -II 和血管加压素并不抑制内皮依赖性和非内皮依赖性舒张。这些结果表明，内皮素 -1 不仅会引起脑血管收缩，还会干扰血管舒张机制，并且内皮依赖性血管舒张比非内皮依赖性血管舒张对内皮素 -1 的抑制作用更敏感。
