Sobey C G, Heistad D D, Faraci F M
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):H126-32. doi: 10.1152/ajpheart.1996.271.1.H126.
Cerebral vasodilator responses are often impaired following subarachnoid hemorrhage (SAH). Because depolarization of vascular muscle may occur after SAH, we tested in vivo the hypothesis that SAH may augment dilatation in response to hyperpolarization due to activation of K+ channels. Anesthetized rats were studied two days after injection of saline or autologous blood into the cisterna magna. Diameter of the basilar artery in vivo was 224 +/- 5 microns (mean +/- SE) in saline-treated rats and 201 +/- 6 microns in SAH rats (P < 0.05). In control rats, acetylcholine (ACh), sodium nitroprusside (SNP), aprikalim and calcitonin gene-related peptide (CGRP; both activators of ATP-sensitive K+ channels), papaverine, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), and brain natriuretic peptide (BNP; an activator of particulate guanylate cyclase) produced concentration-dependent dilatation. In SAH rats, vasodilatation was impaired in response to ACh and SNP. In contrast, vasodilator responses to aprikalim and CGRP were augmented in SAH, rats (by two- to fourfold). Vasodilator responses to 8-BrcGMP, papaverine, and BNP were similar in both groups. Thus responses mediated by activation of soluble guanylate cyclase are selectively impaired by SAH, but responses to guanosine 3',5'-cyclic monophosphate are normal. Vasodilator responses to activation of ATP-sensitive K+ channels are augmented by SAH.
蛛网膜下腔出血(SAH)后,脑血管舒张反应常受损。由于SAH后血管平滑肌可能发生去极化,我们在体内测试了SAH可能因钾通道激活而增强对超极化反应的扩张这一假说。在向大鼠脑池内注射生理盐水或自体血两天后,对麻醉大鼠进行研究。生理盐水处理的大鼠体内基底动脉直径为224±5微米(平均值±标准误),SAH大鼠为201±6微米(P<0.05)。在对照大鼠中,乙酰胆碱(ACh)、硝普钠(SNP)、阿普卡林和降钙素基因相关肽(CGRP;两者均为ATP敏感性钾通道激活剂)、罂粟碱、8-溴鸟苷3',5'-环磷酸(8-BrcGMP)和脑钠肽(BNP;颗粒型鸟苷酸环化酶激活剂)产生浓度依赖性扩张。在SAH大鼠中,对ACh和SNP的血管舒张反应受损。相反,SAH大鼠对阿普卡林和CGRP的血管舒张反应增强(增加了两到四倍)。两组对8-BrcGMP、罂粟碱和BNP的血管舒张反应相似。因此,SAH选择性损害可溶性鸟苷酸环化酶激活介导的反应,但对鸟苷3',5'-环磷酸的反应正常。SAH增强了对ATP敏感性钾通道激活的血管舒张反应。