降钙素基因相关肽诱导大鼠冠状动脉舒张过程中内皮的异质性参与。
Heterogeneous involvement of endothelium in calcitonin gene-related peptide-induced relaxation in coronary arteries from rat.
作者信息
Prieto D, Benedito S, Nyborg N C
机构信息
Department of Pharmacology, University of Aarhus, Denmark.
出版信息
Br J Pharmacol. 1991 Jul;103(3):1764-8. doi: 10.1111/j.1476-5381.1991.tb09860.x.
Abstract
- The effects of rat- and human-CGRP and capsaicin were studied in isolated rings of rat proximal epicardial (PC) and distal intramyocardial (DC) coronary arteries. 2. The relaxing effect of rat-CGRP was dependent on the level of vessel tone induced by prostaglandin F2 alpha (PGF2 alpha) in PC but not in DC arteries. Submaximally contracted DC and PC arteries were more sensitive to rat- than human-CGRP. There was no difference in sensitivity to rat- and human-CGRP between PC and DC arteries. 3. Substance P elicited a small relaxation only in 4 of the 6 PC arteries tested. PC and DC arteries were concentration-dependently relaxed by capsaicin. The relaxation was partly inhibited by ruthenium red, thus suggesting that capsaicin causes specific release of CGRP from sensory nerve endings in rat coronary arteries. 4. The relaxant effect of rat-CGRP was antagonized by endothelium removal and indomethacin but not methylene blue in endothelium-intact PC arteries. The relaxation in DC arteries was not affected by any of these treatments, indicating a heterogeneous involvement of the endothelium in CGRP-mediated coronary vasodilatation and the release of a cyclo-oxygenase product in PC arteries in rats. 5. Glibenclamide had no inhibitory effect on the CGRP-induced relaxation of PC and DC arteries, thus excluding the involvement of glibenclamide-sensitive K(+)-channels in the mechanism of action of CGRP in rat coronary arteries.
摘要
- 研究了大鼠和人降钙素基因相关肽（CGRP）及辣椒素对大鼠近端心外膜（PC）和远端心肌内（DC）冠状动脉离体血管环的作用。2. 大鼠CGRP的舒张作用取决于前列腺素F2α（PGF2α）在PC动脉而非DC动脉中诱导的血管张力水平。亚最大收缩的DC和PC动脉对大鼠CGRP比人CGRP更敏感。PC和DC动脉对大鼠和人CGRP的敏感性无差异。3. 仅在6条受试PC动脉中的4条中，P物质引起轻微舒张。PC和DC动脉被辣椒素浓度依赖性舒张。该舒张部分被钌红抑制，因此提示辣椒素可导致大鼠冠状动脉感觉神经末梢特异性释放CGRP。4. 在完整内皮的PC动脉中，大鼠CGRP的舒张作用被去除内皮和吲哚美辛拮抗，但不被亚甲蓝拮抗。DC动脉中的舒张不受这些处理的任何影响，表明内皮在CGRP介导的冠状动脉舒张中的参与存在异质性，且大鼠PC动脉中有环氧化酶产物释放。5. 格列本脲对CGRP诱导的PC和DC动脉舒张无抑制作用，因此排除了格列本脲敏感的钾通道参与大鼠冠状动脉中CGRP作用机制。
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