The α1-adrenoceptor antagonist, doxazosin, modulates the lower limit of autoregulation of cerebral blood flow during hemorrhagic hypotension in anesthetized hypertensive rats

Abstract

The objective of the present study was to examine the effects of administration of an α 1-adrenoceptor antagonist, doxazosin, for 7 days on cerebral blood flow and the autoregulatory response to hypotension in anesthetized spontaneously hypertensive rats. We determined cerebral blood flow at rest and during hemorrhagic hypotension in 14 rats of each group using laser-Doppler flowmetry, and at the same time, the absolute baseline cerebral blood flow values at the parietal cortex were also quantified in some of the rats with the hydrogen clearance method. Baseline mean arterial pressure was significantly lowered, by 41 mm Hg, in the doxazosin-treated group, while the baseline cerebral blood flow was 31 ± 4 ml/100 g/min (mean ± S.D.) which was almost the same as the 32 ± 5 ml/100 g/min in the control group. The lower limits of cerebral blood flow autoregulation were 139 ± 9 mm Hg in the control group and 96 ± 12 mm Hg in the treated group; the difference was significant ( P < 0.001). The present results demonstrated that the lower limit of cerebral blood flow autoregulation shifts to a lower level after chronic treatment with doxazosin, an effect which is favorable for the maintenance of cerebral blood flow under hypotensive conditions.