John W Harrell1, Garrett L Peltonen1,2, William G Schrage1. 1. Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin. 2. Department of Kinesiology, Western New Mexico University, Silver City, New Mexico.
Abstract
AIM: The role of reactive oxygen species (ROS) in human cerebral blood flow (CBF) during hypoxia is largely unknown. Additionally, it is unknown whether ROS interact with cyclooxygenase-derived signals during hypoxia to increase CBF. We hypothesized ROS inhibition would reduce hypoxic CBF, and combined inhibition of cyclooxygenase (COX) and ROS would decrease hypoxic CBF more than ROS suppression alone. METHODS: We measured middle cerebral artery velocity with transcranial Doppler ultrasound in 12 healthy adults during normoxia and 2 isocapnic hypoxia trials. Intravenous ascorbic acid infusion during the first hypoxia trial suppressed ROS. Oral indomethacin inhibited COX between hypoxia trials. The second bout of hypoxia tested the combined effects of ROS and COX inhibition. Middle cerebral artery velocity was normalized for blood pressure as cerebrovascular conductance index. RESULTS: Hypoxia increased cerebrovascular conductance index in both trials (P < 0.05). Ascorbic acid infusion did not alter cerebrovascular conductance index during hypoxia. Combined ascorbic acid and indomethacin significantly reduced hypoxia-mediated increases in cerebrovascular conductance index from 17 ± 2 to 4 ± 1 cm s-1 100 mm Hg-1 (P < 0.05). CONCLUSION: ROS are not obligatory for hypoxic cerebral vasodilation. Current data indicate ROS and COX together may account for the majority of the increase in CBF through the middle cerebral artery during hypoxia. These data are the first to demonstrate compensatory hypoxic vasodilatory signalling in human cerebral circulation.
AIM: The role of reactive oxygen species (ROS) in human cerebral blood flow (CBF) during hypoxia is largely unknown. Additionally, it is unknown whether ROS interact with cyclooxygenase-derived signals during hypoxia to increase CBF. We hypothesized ROS inhibition would reduce hypoxic CBF, and combined inhibition of cyclooxygenase (COX) and ROS would decrease hypoxic CBF more than ROS suppression alone. METHODS: We measured middle cerebral artery velocity with transcranial Doppler ultrasound in 12 healthy adults during normoxia and 2 isocapnic hypoxia trials. Intravenous ascorbic acid infusion during the first hypoxia trial suppressed ROS. Oral indomethacin inhibited COX between hypoxia trials. The second bout of hypoxia tested the combined effects of ROS and COX inhibition. Middle cerebral artery velocity was normalized for blood pressure as cerebrovascular conductance index. RESULTS:Hypoxia increased cerebrovascular conductance index in both trials (P < 0.05). Ascorbic acid infusion did not alter cerebrovascular conductance index during hypoxia. Combined ascorbic acid and indomethacin significantly reduced hypoxia-mediated increases in cerebrovascular conductance index from 17 ± 2 to 4 ± 1 cm s-1 100 mm Hg-1 (P < 0.05). CONCLUSION:ROS are not obligatory for hypoxic cerebral vasodilation. Current data indicate ROS and COX together may account for the majority of the increase in CBF through the middle cerebral artery during hypoxia. These data are the first to demonstrate compensatory hypoxic vasodilatory signalling in human cerebral circulation.
Authors: J Mikhail Kellawan; Garrett L Peltonen; John W Harrell; Alejandro Roldan-Alzate; Oliver Wieben; William G Schrage Journal: Am J Physiol Regul Integr Comp Physiol Date: 2019-12-23 Impact factor: 3.619
Authors: Katrina J Carter; Aaron T Ward; J Mikhail Kellawan; Marlowe W Eldridge; Awni Al-Subu; Benjamin J Walker; Jeffrey W Lee; Oliver Wieben; William G Schrage Journal: J Physiol Date: 2021-10-13 Impact factor: 6.228