Contraction of diabetic rabbit aorta caused by endothelium-derived PGH2-TxA2.
Contraction of diabetic rabbit aorta caused by endothelium-derived PGH2-TxA2.
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DOI：
10.1152/ajpheart.1989.257.5.h1327
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发表时间：
1989-11
期刊：
影响因子：
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通讯作者：
B. Tesfamariam;J. Jakubowski;Richard A. Cohen
中科院分区：
文献类型：
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作者：
B. Tesfamariam;J. Jakubowski;Richard A. Cohen
在四氧嘧啶诱导的糖尿病家兔动脉中，测定了乙酰胆碱引起的内皮依赖性舒张和血管活性前列腺素样物质的产生。糖尿病兔主动脉，苯肾上腺素次最大收缩，显示明显减少内皮依赖性舒张由乙酰胆碱诱导与正常兔的主动脉相比。吲哚美辛，环氧合酶抑制剂，和SQ 29548，前列腺素H2-血栓烷A2（PGH 2-TxA 2）受体拮抗剂，正常化的敏感性糖尿病性阿托伐他汀乙酰胆碱，而这些药物对正常阿托伐他汀的反应没有影响。舒张反应的非受体介导的内皮依赖性血管舒张剂，A23187，和内皮非依赖性血管舒张剂，硝普钠，正常和糖尿病患者之间没有什么不同。乙酰胆碱还引起糖尿病兔的静息主动脉环与内皮的收缩，但不正常;这些收缩被吲哚美辛抑制。合成的TxA 2，测定为免疫反应TxB 2，显着增加，只有当内皮细胞在糖尿病主动脉段。这些结果表明，在糖尿病状态下，内皮释放主要的血管收缩剂环氧合酶产物，其直接抵消由胆碱能受体刺激诱导的内皮源性舒张因子的释放引起的舒张或选择性干扰内皮源性舒张因子的释放。血管收缩剂很可能是TxA 2或其前体PGH 2。
Endothelium-dependent relaxations and vasoactive prostanoid production caused by acetylcholine were determined in the aortas of rabbits with diabetes mellitus induced by alloxan. Aortas of diabetic rabbits, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with the aortas of normal rabbits. Indomethacin, a cyclooxygenase inhibitor, and SQ 29548, a prostaglandin H2-thromboxane A2 (PGH2-TxA2) receptor antagonist, normalized the sensitivity of diabetic aortas to acetylcholine, whereas these agents had no effect on the response of normal aortas. The relaxations in response to a nonreceptor-mediated endothelium-dependent vasodilator, A23187, and an endothelium-independent vasodilator, sodium nitroprusside, were not different between normal and diabetic aortas. Acetylcholine also caused contractions of resting aortic rings with endothelium from diabetic, but not normal rabbits; these contractions were inhibited by indomethacin. Synthesis of TxA2, measured as immunoreactive TxB2, was significantly increased in diabetic aortic segments only when the endothelium was present. These results suggest that in the diabetic state, the endothelium releases a major vasoconstrictor cyclooxygenase product that either directly counteracts the relaxation caused by or selectively interferes with the release of endothelium-derived relaxing factor(s) induced by cholinergic receptor stimulation. The vasoconstrictor is most likely TxA2 or possibly its precursor, PGH2.