Interaction of endothelium with dilation produced by inhibitors of cyclic nucleotide diesterases in mouse brain arterioles in vivo.
Interaction of endothelium with dilation produced by inhibitors of cyclic nucleotide diesterases in mouse brain arterioles in vivo.
复制标题
内皮细胞与体内小鼠脑小动脉环核苷酸二酯酶抑制剂产生的扩张的相互作用。
DOI：
10.1161/01.str.24.2.266
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发表时间：
1993
期刊：
影响因子：
8.3
通讯作者：
Nelson,GH
中科院分区：
文献类型：
--
作者：
Rosenblum,WI;Shimizu,T;Nelson,GH
从脑外传导血管收集的体外证据表明，血管平滑肌中的内皮源性乙酰胆碱舒张因子（EDRFACH）和环核苷酸作用之间存在相互作用。本研究的目的是在体内软膜小动脉中检查这种相互作用。与体外实验一样，我们使用磷酸二酯酶抑制剂来提高血管平滑肌中环核苷酸的水平，用电视显微镜观察小鼠软脑膜血管。采用图像分割技术监测小动脉的直径。在局灶性内皮损伤之前和之后或在应用N-胍基-L-单甲基精氨酸（L-NMMA）之前和期间测试了对局部应用的磷酸二酯酶抑制剂的反应。已知这两种治疗方法都能消除该制剂中对乙酰胆碱的内皮依赖性反应。磷酸二酯酶抑制剂可扩张软脑膜小动脉。这对于磷酸二酯酶抑制剂升高腺苷3 '，5'-环一磷酸（cAMP）和鸟苷3 '，5'-环一磷酸（cGMP）的水平以及对于被认为选择性地影响任一核苷酸的抑制剂是真实的。内皮损伤和L-NMMA抑制扩张。数据表明，脑小动脉扩张的cAMP和cGMP，但如果EDRFACh水平降低，这种作用受损。由于EDRFACH升高cGMP水平，这些数据支持cGMP和cAMP的舒张作用取决于血管平滑肌中cGMP的足够基础水平的假设。这一假说最初是在体外脑外传导动脉的研究中提出的，现在可以应用于体内脑阻力血管。
In vitro evidence gathered from extracerebral conductance vessels suggests interaction between the endothelium-derived relaxing factor for acetylcholine (EDRFACh) and cyclic nucleotide action in vascular smooth muscle. The purpose of this study was to examine this interaction in vivo in pial arterioles. As had been done in vitro, we used phosphodiesterase inhibitors that elevate cyclic nucleotide levels in vascular smooth muscle.Pial vessels of mice were observed with television microscopy. Diameter of the arterioles was monitored with an image-splitting technique. The responses to topically applied phosphodiesterase inhibitors were tested before and after focal endothelial injury or before and during application of N-guanidino-L-monomethyl arginine (L-NMMA). Both treatments are known to eliminate the endothelium-dependent response to acetylcholine in this preparation.Phosphodiesterase inhibitors dilated pial arterioles. This was true for phosphodiesterase inhibitors elevating levels of both adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) as well as for inhibitors thought to selectively affect either nucleotide. The dilation was inhibited by endothelial injury and by L-NMMA.The data suggest that brain arterioles are dilated by both cAMP and cGMP but that this action is impaired if EDRFACh levels are reduced. Since EDRFACh elevates cGMP levels, these data support the hypothesis that the relaxing actions of cGMP and cAMP depend upon adequate basal levels of cGMP in vascular smooth muscle. This hypothesis, originally introduced in studies of extracerebral conductance arteries in vitro, can now be applied to brain resistance vessels in vivo.