Barry D I, Paulson O B, Jarden J O, Juhler M, Graham D I, Strandgaard S
Am J Med. 1984 May 31;76(5B):79-85. doi: 10.1016/0002-9343(84)90890-8.
Cerebrovascular effects of the angiotensin converting enzyme inhibitor captopril were examined in normotensive and hypertensive rats. Cerebral blood flow was measured with the intracarotid 133xenon injection method in halothane-anesthetized animals. The blood-brain barrier permeability of captopril (determined with an integral-uptake method) was negligible, the permeability-surface area product in most brain regions being 1 X 10(-5) cm3/g per second, that is, three to four times lower than that of sodium ion. When administered into the cerebral ventricles to bypass the blood-brain barrier, captopril had no effect on cerebral blood flow: furthermore, cerebral blood flow autoregulation (studied by raising and lowering blood pressure) was identical to that in controls. In contrast, when given intravenously, captopril had a marked effect on cerebral blood flow autoregulation--both the lower and upper limits of autoregulation being shifted to a lower pressure (by about 20 to 30 and 50 to 60 mm Hg, respectively), and the autoregulatory range was shortened by about 40 mm Hg. This effect may be ascribed to inhibition of converting enzyme in the cerebral blood vessels rather than within the brain.
在正常血压和高血压大鼠中研究了血管紧张素转换酶抑制剂卡托普利对脑血管的影响。采用颈内动脉注射133氙的方法,在氟烷麻醉的动物中测量脑血流量。卡托普利的血脑屏障通透性(用整体摄取法测定)可忽略不计,大多数脑区的通透表面积乘积为每秒1×10(-5)cm3/g,即比钠离子的通透表面积乘积低三到四倍。当经脑室给药以绕过血脑屏障时,卡托普利对脑血流量无影响;此外,脑血流量自动调节(通过升高和降低血压进行研究)与对照组相同。相比之下,静脉给药时,卡托普利对脑血流量自动调节有显著影响——自动调节的下限和上限均移至较低压力(分别降低约20至30和50至60 mmHg),自动调节范围缩短约40 mmHg。这种效应可能归因于对脑血管而非脑内转换酶的抑制。