Supernatants prepared from the rabbit brain, lung and liver caused an endothelium-dependent and volume-related contraction of the phenylephrine-pretreated rabbit aorta and inhibited relaxation due to acetylcholine (ACh). 2. Perfusion in situ of the rabbit lung or liver with Krebs solution substantially reduced or removed the endothelium-dependent inhibitor. Spectrophotometric analysis revealed the presence of substantial amounts of haemoglobin (1.8-2.1 microM) in these organ supernatants. 3. Supernatants prepared from the Krebs-perfused rabbit brain retained the ability to contract the phenylephrine-pretreated rabbit aorta and to inhibit relaxation due to ACh and substance P (SP). Rabbit brain supernatant did not reduce the vasodilator effect of sodium nitroprusside (NP) or nitric oxide (NO). 4. Rabbit brain supernatant contained low (less than 0.35 microM) concentrations of haemoglobin. 5. The inhibitory effect of rabbit brain supernatant was reversed by L-arginine (500 microM) but not D-arginine (500 microM). 6. The inhibitor of endothelium-dependent vasodilatation present in rabbit brain was not removed by dialysis (24 h, 4 degrees C) but was partially precipitated by ammonium sulphate (30% w/v). 7. Rabbit brain contains an endogenous inhibitor of vascular NO biosynthesis. The identity of this inhibitor is not known although it seems likely to be a large peptide or protein.
摘要
从兔脑、肺和肝脏制备的上清液可引起经去氧肾上腺素预处理的兔主动脉出现内皮依赖性和容量相关的收缩,并抑制乙酰胆碱(ACh)所致的舒张。2. 用 Krebs 溶液对兔肺或肝脏进行原位灌注可大幅降低或消除内皮依赖性抑制剂。分光光度分析显示这些器官上清液中存在大量血红蛋白(1.8 - 2.1 μM)。3. 用 Krebs 溶液灌注的兔脑制备的上清液仍具有使经去氧肾上腺素预处理的兔主动脉收缩以及抑制 ACh 和 P 物质(SP)所致舒张的能力。兔脑上清液不会降低硝普钠(NP)或一氧化氮(NO)的血管舒张作用。4. 兔脑上清液中血红蛋白浓度较低(低于 0.35 μM)。5. L - 精氨酸(500 μM)可逆转兔脑上清液的抑制作用,而 D - 精氨酸(500 μM)则不能。6. 兔脑中存在的内皮依赖性血管舒张抑制剂不能通过透析(24 小时,4℃)去除,但可被硫酸铵(30% w/v)部分沉淀。7. 兔脑含有一种内源性血管 NO 生物合成抑制剂。尽管这种抑制剂似乎可能是一种大肽或蛋白质,但其具体身份尚不清楚。