Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow with Exposure to Intermittent Hypoxia in Humans
Date
2013-04-23
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Abstract
Background: Intermittent hypoxia (IH) simulating obstructive sleep apnea raises blood pressure (BP) and impairs cerebral blood flow response. The pathophysiology of intermittent hypoxia-mediated increase in BP involves multiple mechanisms but the role of cyclooxygenase (COX) catalyzed vasoactive prostaglandins (PG) is unclear.
Methods: A placebo controlled double-blind randomized cross-over trial was designed using nonselective COX inhibitor indomethacin (50 mg tid/po), selectively COX-2 inhibitor celecoxib (200 mg bid/po) comparing with placebo. Healthy males ingested either of drugs for 4 days and physiological measurements were taken on 5th day with an acute isocapnic-hypoxia challenge pre- and post 6 hrs of IH exposure. Urinary PGs were assayed pre- and post- IH exposure.
Results: After 4 days of drug, INDO increased BP compared to PLBO and CLBX; and lowered CBF compared to PLBO (air and baseline breathing). Mean arterial pressure gain with INDO increased followed by CLBX in response to acute isocapnic hypoxia and it was driven by increased gains in both systolic BP and diastolic BP (statistically not significant). CBF gain was blunted with CLBX while it was similar between INDO and PLBO although they were not statistically significant. With 6 hrs of IH (post-IH), CBF gain remained blunted with CLBX but was augmented with INDO (statistically not significant). CVC gain was lower with CLBX (statistically not significant). Both drugs lowered vasodilator and vasoconstrictor PGs compared to PLBO. Pre-IH PGI2:TxA2 was higher with INDO compared to PLBO (p < 0.001) and CLBX (p < 0.001).
Conclusion: Indomethacin perturbs cardio- and cerebrovascular homeostasis in more robust manner as compared to placebo and celecoxib after 4 days of ingestion.
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Neuroscience
Citation
Pun, M. (2013). Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow with Exposure to Intermittent Hypoxia in Humans (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25809