PROSTANOID CASCADE INHIBITION PREVENTS CARDIOVASCULAR AND ADRENOCORTICOTROPIC RESPONSES TO MINERAL ACID INFUSION

Mineral acid infusion is used to investigate the effects of acidemia o n the cardiovascular and respiratory systems. Previous studies have sh own that small infusions of HCl increase mean arterial pressure (MAP), adrenocorticotropic hormone (ACTH), and cortisol without producing ac idemia. 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). Ac id 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), sodi um (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 T xA2) (147 +/- 78 to 2,304 +/- 1,213 pg/ml), whereas these changes were prevented by flunixin. Plasma concentrations of 6-ketoprostaglandin F 1alpha (stable metabolite of prostacyclin), prostaglandin E2, interleu kin-1alpha, and hematocrit did not change in either group. Arterial pH decreased, whereas arterial partial pressure of CO2 increased signifi cantly in both groups. Arterial partial pressure of O2 declined in bot h 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 respons es to mineral acid infusion.