AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 6 1235-R1241, Copyright © 1993 by American Physiological Society
Prostanoid cascade inhibition prevents cardiovascular and adrenocorticotropic responses to mineral acid infusion
T. A. Cudd and C. E. Wood
Department of Physiology, University of Florida, Gainesville 32610.
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.
