Angiotensin II contributes to cerebral vasodilatation during hypoxia in the rabbit.

BACKGROUND

and Purpose 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 = 11), rabbits were subjected to 30 minutes of stable hypoxia (PaO2 = 34 +/- 1 mm Hg, mean +/- SD) followed by 15 minutes of reoxygenation (PaO2 = 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 = 11), blood flow was measured as in the previous group except that an infusion of the angiotensin II receptor antagonist saralasin (1 microgram.kg-1.min-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 = 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 = 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 +/- 15 mL.min-1.100 g-1. During hypoxia, CBF increased to a greater extent in the absence versus the presence of saralasin (95 +/- 31 and 104 +/- 30 mL.min-1.100 g-1 versus 72 +/- 24 and 71 +/- 25 mL.min-1.100 g-1, respectively; P = .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 +/- 24 and 89 +/- 16 mL.min-1.100 g-1 versus 72 +/- 16 and 73 +/- 17 mL.min-1.100 g-1). To rule out the possibility that saralasin produced non-specific 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 +/- 17 and 64 +/- 6 mL.min-1.100 g-1, respectively; P > .05). Hypercapnia increased CBF similarly in the absence and presence of saralasin (81 +/- 22 and 91 +/- 19 mL.min-1.100 g-1; PaCO2 = 61 +/- 2 and 60 +/- 2 mm Hg, respectively; P > .05).

CONCLUSIONS

Because the ACE inhibitor captopril and the angiotensin II receptor blocker saralasin attenuated increased in CBF during hypoxia, the findings suggest that endogenous release of angiotensin II contributes to the increase in CBF during hypoxia.