ATTENUATION AND RECOVERY OF BRAIN-STEM AUTOREGULATION IN SPONTANEOUSLY HYPERTENSIVE RATS

Cerebral large arteries dilate actively around the lower limits of CBF autoregulation, mediated at least partly by nitric oxide, and maintai n CBF during severe hypotension. We tested the hypothesis that this au toregulatory response of large arteries, as well as the response of ar terioles, is altered in spontaneously hypertensive rats (SHR) and that the altered response reverts to normal during long-term antihypertens ive treatment with cilazapril, an angiotensin-converting enzyme inhibi tor. In anesthetized 6- to 7-month-old normotensive Wistar-Kyoto rats (WKY), 4- and 6- to 7-month-old SHR without antihypertensive treatment , and 6- to 7-month-old SHR treated with cilazapril for 10 weeks, loca l CBF to the brain stem was determined with laser-Doppler flowmetry an d diameters of the basilar artery and its branches were measured throu gh a cranial window during stepwise hemorrhagic hypotension. The lower limit of CBF autoregulation shifted upward in untreated SHR to 90 to 105 mm Hg from 30 to 45 mm Hg in WKY, and it reverted to 30 to 45 mm H g in treated SHR. In response to severe hypotension, the basilar arter y dilated by 21 +/- 6% (mean +/- SD) of the baseline internal diameter in WKY. The vasodilation was impaired in untreated SHR (10 +/- 8% in 4-mo-old SHR and 4 +/- 5% in 6- to 7-month-old SHR), and was restored to 22 +/- 10% by treatment with cilazapril (P < 0.005). Dilator respon ses of branch arterioles to hypotension showed similar attenuation and recovery as that of the basilar artery. The data indicate that chroni c hypertension impairs the autoregulatory dilation of the basilar arte ry as well as branch arterioles and that antihypertensive treatment wi th cilazapril restores the diminished dilation toward normal.