Thromboxane A2 acts on the brain to mediate hemodynamic, adrenocorticotropin, and cortisol responses.
Conditions that increase the formation of thromboxane A2 (TxA2) also result in activation of hemodynamic and adrenocortical responses. The purpose of this study was to test the hypothesis that TxA2 acts directly on the brain to mediate these responses. Adult sheep were chronically instrumented with vascular and intracerebroventricular catheters. The TxA2 analog U-46619 (0, 100, or 1,000 ng.kg-1.min-1) and artificial cerebrospinal fluid (CSF) were infused intracerebroventricularly for 30 min. Heart rate increased in response to 100 ng.kg-1.min-1 U-46619 infusions. Heart rate did not change over preinfusion values in response to the highest infusion rate, but values were elevated compared with the postinfusion period. Mean arterial pressure, ACTH, cortisol, hematocrit, and arterial pH (pHa) increased, and arterial partial CO2 pressure (PaCO2) fell in response to 1,000 ng.kg-1.min-1 infusions of U-46619. Plasma vasopressin concentrations and arterial partial O2 pressure did not change. In a second study, U-46619 or artificial CSF was infused intracerebroventricularly during prostaglandin synthase blockade. Blockade reduced but did not prevent blood pressure responses to U-46619 infusion, suggesting that the U-46619 infusions increased prostaglandin synthase metabolism to contribute de novo TxA2 or a second metabolite to augment the blood pressure response. Heart rate, pHa, PaCO2, ACTH, and cortisol responses to U-46619 were not different with blockade. We conclude that TxA2 acts on the brain to mediate blood pressure, heart rate, pHa, PaCO2, hematocrit, ACTH, and cortisol responses. These findings support the hypothesis that TxA2 acts directly on the brain to promote cardiovascular and hormonal responses that may serve a protective function during conditions when TxA2 formation is increased.
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006854:Hydrocortisone / Q000502:physiology*; D010902:Pituitary Gland / Q000502:physiology*; D012756:Sheep; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone