Hypoxia increases cerebral blood flow (CBF). Hypoxia also exerts a major influence on the renin-angiotensin system. In addition to the circulating renin-angiotensin system, a local renin-angiotensin system appears to be present in the brain, and angiotensin II receptors have been identified in cerebral blood vessels. In this study we tested the hypothesis that endogenous angiotensin II attenuates dilatation of the cerebral vessels during hypoxia. Methods Pentobarbital-anesthetized rabbits were prepared for measurement of blood flow (microspheres) and assigned to one of two groups: in group 1 (n equals 11), rabbits were subjected to 30 minutes of stable hypoxia (PaO2 equals 34 plus minus 1 mm Hg, mean plus minus SD) followed by 15 minutes of reoxygenation (Pao sub 2 equals 177 to 200 mm Hg). Blood flow was measured four times: under control conditions, after 15 and 30 minutes of hypoxia, and after 15 minutes of reoxygenation. This was a control group to characterize changes in CBF during hypoxia. In group 2 (n equals 11), blood flow was measured as in the previous group except that an infusion of the angiotensin II receptor antagonist saralasin (1 mu g centered dot kgminus 1 centered dot minminus 1 IV) was started with the onset of hypoxia and continued through reoxygenation to the end of the experiment. The goal of this group was to examine whether endogenous activation of receptors for angiotensin II influences increases in CBF during hypoxia. In a separate series of experiments we examined the influence of the angiotensin-converting enzyme (ACE) inhibitor captopril on the hypoxic response. Thus, in one group of rabbits we measured CBF in the same manner as in group 1 (n equals 13). In another group of rabbits we also measured blood flow as in group 1 except that rabbits received 10 mg/kg of the ACE inhibitor captopril before the control measurement (n equals 11). We tested for significant differences between groups using two-way ANOVA. Results Under control conditions, CBF was similar in all groups and averaged 53 plus minus 15 mL centered dot min sup minus 1 centered dot 100 g sup minus 1. During hypoxia, CBF increased to a greater extent in the absence versus the presence of saralasin (95 plus minus 31 and 104 plus minus 30 mL centered dot minminus 1 centered dot 100 gminus 1 versus 72 plus minus 24 and 71 plus minus 25 mL centered dot minminus 1 centered dot 100 gminus 1, respectively; P equals.003). Increase in CBF during hypoxia was also significantly greater in the animals that did not receive captopril versus those that were treated with captopril (100 plus minus 24 and 89 plus minus 16 mL centered dot minminus 1 centered dot 100 gminus 1 versus 72 plus minus 16 and 73 plus minus 17 mL centered dot minminus 1 centered dot 100 gminus 1). To rule out the possibility that saralasin produced nonspecific attenuation of cerebral vasodilatation, we tested the influence of hypercapnia on CBF in the absence and presence of saralasin. During normocapnia, CBF values were not significantly different in the absence and presence of saralasin (57 plus minus 17 and 64 plus minus 6 mL centered dot minminus 1 centered dot 100 gminus 1, respectively; P more than.05). Hypercapnia increased CBF similarly in the absence and presence of saralasin (81 plus minus 22 and 91 plus minus 19 mL centered dot minminus 1 centered dot 100 gminus 1; Paco2 equals 61 plus minus 2 and 60 plus minus 2 mm Hg, respectively; P more than.05). Conclusions Because the ACE inhibitor captopril and the angiotensin II receptor blocker saralasin attenuated increases in CBF during hypoxia, the findings suggest that endogenous release of angiotensin II contributes to the increase in CBF during hypoxia.