Sobey C G, Quan L
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3052, Australia.
Am J Physiol. 1999 Nov;277(5):H1718-24. doi: 10.1152/ajpheart.1999.277.5.H1718.
Subarachnoid hemorrhage (SAH) is associated with impaired nitric oxide (NO)-mediated cerebral vasodilatation. We tested the hypothesis that SAH causes alterations in the production of, hydrolysis of, or responsiveness to cGMP in the rat basilar artery in vivo. Rats were injected with saline or autologous blood into the cisterna magna. Two days later, effects of vasoactive drugs on basilar artery diameter were examined using a cranial window preparation. Vasodilator responses to ACh, sodium nitroprusside (SNP), and low concentrations (</=10(-5) M) of zaprinast, an inhibitor of phosphodiesterase V (PDE V), were impaired in SAH rats (P < 0.05). In contrast, vasodilator responses to adenosine and 8-BrcGMP were similar in control and SAH rats. Vasoconstrictor responses to 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, were unaffected by SAH. In the presence of zaprinast (10(-5)-10(-4) M), responses to ACh and SNP were equivalent in control and SAH rats. Thus an increased rate of cGMP hydrolysis by PDE V may be a major factor contributing to the impairment of NO-mediated cerebral vasodilatation after SAH.
蛛网膜下腔出血（SAH）与一氧化氮（NO）介导的脑血管舒张功能受损有关。我们检验了这样一个假说：SAH会导致大鼠体内基底动脉中cGMP的生成、水解或反应性发生改变。将大鼠的枕大池注射生理盐水或自体血。两天后，使用颅骨开窗制剂检查血管活性药物对基底动脉直径的影响。SAH大鼠对乙酰胆碱（ACh）、硝普钠（SNP）以及磷酸二酯酶V（PDE V）抑制剂扎普司特低浓度（≤10⁻⁵ M）的血管舒张反应受损（P < 0.05）。相比之下，对照组和SAH大鼠对腺苷和8-溴环鸟苷酸（8-BrcGMP）的血管舒张反应相似。SAH对可溶性鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3,-a]喹喔啉-1-酮的血管收缩反应没有影响。在扎普司特（10⁻⁵ - 10⁻⁴ M）存在的情况下，对照组和SAH大鼠对ACh和SNP的反应相当。因此，PDE V导致的cGMP水解速率增加可能是SAH后NO介导的脑血管舒张功能受损的一个主要因素。
