Prostanoid cascade inhibition prevents cardiovascular and adrenocorticotropic responses to mineral acid infusion.
Mineral acid infusion is used to investigate the effects of acidemia on the cardiovascular and respiratory systems. Previous studies have shown that small infusions of HCl increase mean arterial pressure (MAP), adrenocorticotropic hormone (ACTH), and cortisol without producing acidemia. We infused 1 meq/min of 1 N HCl intravenously into chronically catheterized conscious sheep with or without pretreatment with 1.1 mg/kg flunixin-N-methylglucamine, a cyclooxygenase inhibitor (n = 6). Acid infusion resulted in significant increases in heart rate (83 +/- 5 to 94 +/- 7 beats/min), MAP (84 +/- 3 to 104 +/- 6 mmHg), ACTH (97 +/- 23 to 285 +/- 101 pg/ml), cortisol (20 +/- 3 to 37 +/- 16 ng/ml), sodium (149.5 +/- 0.8 to 150.6 +/- 1.3 meq/l), potassium (3.96 +/- 0.09 to 4.31 +/- 0.19 meq/l), and thromboxane (Tx) B2 (stable metabolite of TxA2) (147 +/- 78 to 2,304 +/- 1,213 pg/ml), whereas these changes were prevented by flunixin. Plasma concentrations of 6-ketoprostaglandin F1 alpha (stable metabolite of prostacyclin), prostaglandin E2, interleukin-1 alpha, and hematocrit did not change in either group. Arterial pH decreased, whereas arterial partial pressure of CO2 increased significantly in both groups. Arterial partial pressure of O2 declined in both groups, but the decrease was significantly greater in the group not receiving flunixin. We conclude that a cyclooxygenase metabolite, most likely TxA2, mediates the MAP, heart rate, ACTH, and cortisol responses to mineral acid infusion.
Department of Physiology, University of Florida, Gainesville 32610.
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D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001158:Arteries; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D006863:Hydrogen-Ion Concentration; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000097:blood; D012756:Sheep
D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D000324:Adrenocorticotropic Hormone; D006851:Hydrochloric Acid; D006854:Hydrocortisone