Thromboxane A2 receptor antagonism prevents hormonal and cardiovascular responses to mineral acid infusion.
Small infusions of strong acid create large elevations in heart rate (HR), mean arterial pressure (MAP), adrenocorticotropic hormone (ACTH), cortisol, and thromboxane A2 (TxA2). We hypothesized that TxA2 is responsible for these hormonal and hemodynamic responses. Conscious sheep received HCl (1 N, 1 ml/min for 30 min) with or without receiving SQ-29548 [a TxA2/prostaglandin (PG) H2 receptor antagonist]. HCl increased TxB2 from 133 +/- 44 to 1,213 +/- 531 (SE) pg/ml while SQ-29548 + HCl increased TxB2 from 141 +/- 41 to 1,051 +/- 518 pg/ml. HCl decreased pH (7.464 +/- 0.015 to 7.413 +/- 0.011), arterial PCO2 (31.6 +/- 1.3 to 25.9 +/- 1.8 mmHg), and arterial PO2 (98.0 +/- 2.2 to 90.5 +/- 3.2 mmHg), and increased MAP (75 +/- 2 to 88 +/- 5 mmHg), HR (72 +/- 4 to 93 +/- 8 beats/min), hematocrit (25 +/- 1 to 29 +/- 2%), ACTH (154 +/- 41 to 549 +/- 217 pg/ml), and aldosterone (25 +/- 1 to 151 +/- 74 pg/ml) while these responses were prevented by SQ-29548. SQ-29548 reduced but did not prevent the cortisol response to HCl (9 +/- 2 to 23 +/- 10 ng/ml compared with 6 +/- 2 to 17 +/- 4 pg/ml after SQ-29548). K+ and aldosterone also increased after the end of SQ-29548 + HCl treatment (4.0 +/- 0.1 to 4.5 +/- 0.1 meq/l and 53 +/- 21 to 147 +/- 61 pg/ml, respectively). We conclude that TxA2 mediates the blood gas, MAP, HR, ACTH, and aldosterone responses to HCl infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Cudd
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Department of Physiology, University of Florida, Gainesville 32610-0274.
Wood
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D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006400:Hematocrit; D006728:Hormones / Q000097:blood / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007262:Infusions, Intravenous; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012756:Sheep; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood*; D013997:Time Factors
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006728:Hormones; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013929:Thromboxane B2; D013928:Thromboxane A2; C045749:SQ 29548; D000324:Adrenocorticotropic Hormone; D006851:Hydrochloric Acid; D006854:Hydrocortisone