Role of α1 adrenergic receptors in the cerebral cortical blood flow response to acute hypoxia in low- and high-altitude near-term fetal lambs.

Fetal cerebral blood flow increases in response to acute hypoxia, mediated in part by an adrenergic α₁ receptor (α₁-R)-mediated increase in peripheral vascular resistance that redirects cardiac output to the brain. Activation of cerebral α₁-R may attenuate the increase in cerebral blood flow during hypoxia, and this effect may be even greater in fetuses exposed to chronic high-altitude hypoxia, which has previously been shown to increase the contractile function of cerebral artery α₁-Rs. We hypothesized that α₁-R activation in the fetal sheep brain attenuates increases in cerebral blood flow during acute hypoxia and that this effect would be accentuated in fetuses exposed to chronic hypoxia. Near-term fetal sheep gestated at low or high altitudes (3,801 m) were instrumented chronically for measurement of mean arterial pressure (MAP), heart rate, cerebral cortical blood flow (CBF), and cortical vascular resistance (CVR). Responses to acute hypoxia were then measured in the presence and absence of prazosin (α₁-R antagonist). Prazosin infusion resulted in a decrease in baseline MAP and CBF. During acute hypoxia, CBF increased by only 14 ± 6% above baseline in the prazosin group, compared with 28 ± 9% in the vehicle group with no significant difference in CVR in either group. Similar to the low-altitude animals, prazosin did not significantly alter the CBF or CVR response to acute hypoxia, nor recovery following acute hypoxia, in the high-altitude fetuses. We conclude that cortical α₁-Rs neither attenuate increased CBF during acute hypoxia nor mediate the cortical vasoconstriction that occurs in recovery from acute hypoxia.NEW & NOTEWORTHY The results of this study indicate that α1-adrenergic receptors on the cerebral vasculature do not mediate cerebral vasoconstriction during acute hypoxic stress, despite a known increase in circulating catecholamine concentrations and sympathetic tone. The same is true for fetuses exposed to chronic hypoxia, which is known to increase the vasocontractile activity of α1-receptors.