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

Abstract

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, previously 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 altitude (3801 m) were instrumented chronically for measurement of mean arterial pressure (MAP), heart rate (HR), 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 to 28±9% in the vehicle group (Fig. 1), 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.