预先暴露于血管收缩剂对大鼠主动脉中异丙肾上腺素诱导的舒张作用的影响：诱导型一氧化氮合酶的参与

Effect of pre-exposure to vasoconstrictors on isoprenaline-induced relaxation in rat aorta: involvement of inducible nitric oxide synthase.

作者信息

Eckly-Michel A, Keravis T, Boudjemaa N, Lugnier C

机构信息

Université Louis Pasteur de Strasbourg, Laboratoire de Pharmacologie et de Physicochimie des Interactions Cellulaires et Moléculaires, UMR-CNRS, B.P. 24, 67401 Illkirch, France.

出版信息

Br J Pharmacol. 1999 Oct;128(3):591-6. doi: 10.1038/sj.bjp.0702840.

DOI:10.1038/sj.bjp.0702840

PMID:10516637

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1571681/

Abstract

The aim of this study was to determine whether a brief (30 min) episode of contractile receptor stimulation could affect the degree of a subsequent vasorelaxation. Therefore, concentration - relaxation curves of the rat aorta to isoprenaline were compared before and after exposure of the tissue to noradrenaline (100 microM) or prostaglandin F2alpha (PGF2alpha, 100 microM). 2. Exposure to noradrenaline enhanced the second maximal relaxant effect of isoprenaline (from 20 - 95% relaxation). This effect was not due to significant differences in precontraction levels and was not modified by the presence of the endothelium. Treatment with PGF2alpha mimicked the actions of noradrenaline on subsequent vasorelaxation to isoprenaline. 3. Before exposure to noradrenaline (100 microM), forskolin (10 microM) did not produce any significant relaxation of the rat aorta. After exposure to noradrenaline, forskolin caused a concentration-dependent relaxation with a maximal effect of more than 90% in rings with and without endothelium suggesting that the change in vasorelaxation to isoprenaline occurred downstream from the beta-adrenoceptor. 4. The increase in relaxation due to exposure to noradrenaline was markedly attenuated by treatment with a protein synthase inhibitor (cycloheximide), a nitric oxide (NO) synthase inhibitor (L-NG-nitroarginine methyl ester, L-NAME) and an inhibitor of the activation of soluble guanylyl cyclase (methylene blue). 5. Western blot analysis showed an increase of inducible NO synthase (iNOS) in aortic rings exposed to noradrenaline or PGF2alpha. 6. Together, these findings suggest that pretreatment of rat aorta with noradrenaline or PGF2alpha could induce vascular NOS which would in turn result in an increase in isoprenaline-induced vasorelaxation, this increase occurring downstream from receptor activation. Such a mechanism might participate in cardioprotection during preconditioning induced by noradrenaline.

摘要

本研究的目的是确定短暂（30分钟）的收缩性受体刺激是否会影响随后血管舒张的程度。因此，在将组织暴露于去甲肾上腺素（100微摩尔）或前列腺素F2α（PGF2α，100微摩尔）之前和之后，比较了大鼠主动脉对异丙肾上腺素的浓度-舒张曲线。2. 暴露于去甲肾上腺素增强了异丙肾上腺素的第二次最大舒张作用（从20%-95%舒张）。这种作用不是由于预收缩水平的显著差异，并且不受内皮存在的影响。用PGF2α处理模拟了去甲肾上腺素对随后对异丙肾上腺素血管舒张的作用。3. 在暴露于去甲肾上腺素（100微摩尔）之前，福斯可林（10微摩尔）不会使大鼠主动脉产生任何显著舒张。暴露于去甲肾上腺素后，福斯可林引起浓度依赖性舒张，在有和没有内皮的环中最大效应超过90%，这表明对异丙肾上腺素血管舒张的变化发生在β-肾上腺素能受体下游。4. 用蛋白质合成抑制剂（环己酰亚胺）、一氧化氮（NO）合酶抑制剂（L-NG-硝基精氨酸甲酯，L-NAME）和可溶性鸟苷酸环化酶激活抑制剂（亚甲蓝）处理，显著减弱了由于暴露于去甲肾上腺素而导致的舒张增加。5. 蛋白质印迹分析显示，暴露于去甲肾上腺素或PGF2α的主动脉环中诱导型NO合酶（iNOS）增加。6. 总之，这些发现表明，用去甲肾上腺素或PGF2α预处理大鼠主动脉可诱导血管NOS，这反过来会导致异丙肾上腺素诱导的血管舒张增加，这种增加发生在受体激活下游。这种机制可能参与去甲肾上腺素诱导的预处理期间的心脏保护。