Indomethacin attenuates the cerebral blood flow response to hypotension in late-gestation fetal sheep.
Previous studies by us and others have demonstrated that PGE(2) and thromboxane (Tx) B(2) are produced in the fetal and neonatal brain during cerebral hypoperfusion. The present study was to test the hypotheses that indomethacin would alter the cerebral blood flow (CBF) response to reduced cerebral perfusion pressure in late-gestation fetal sheep by inhibiting the local prostanoid production. We studied eight chronically catheterized, sinoaortically denervated, 126- to 136-day gestation fetal sheep. The cyclooxygenase inhibitor indomethacin (0.2 mg/kg) or its vehicle phosphate buffer was injected intravenously 90 min before the start of a 10-min period of cerebral hypoperfusion produced by brachiocephalic artery occlusion (BCO). We found that BCO decreased fetal regional CBF (rCBF) by 65-79% in the phosphate buffer group and by 45-57% in the indomethacin-pretreated group. The decrease in fetal rCBF during BCO after indomethacin was 30-49% less than after phosphate buffer. Plasma PGE(2) and TxB(2) concentrations were significantly reduced by indomethacin treatment. BCO increased plasma ACTH and arginine vasopressin (AVP) concentrations; but these responses were not affected by indomethacin. These data suggested that endogenous prostanoid production is involved in the regulation of fetal CBF but, in the absence of intact baro- or chemoreflexes, not in the regulation of ACTH or AVP responses to BCO. We conclude that indomethacin has a beneficial effect on CBF during cerebral ischemia in late-gestation fetal sheep.
Tong
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Department of Physiology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Wood
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CE
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005315:Fetal Diseases / Q000097:blood / Q000503:physiopathology*; D005740:Gases / Q000097:blood; D005865:Gestational Age; D007022:Hypotension / Q000097:blood / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology; D011453:Prostaglandins / Q000097:blood; D012756:Sheep / Q000196:embryology
D016861:Cyclooxygenase Inhibitors; D005740:Gases; D011453:Prostaglandins; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D007213:Indomethacin