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⁻¹U-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 (pH_a) increased, and arterial partial CO₂ pressure (${\text{Pa}}_{{CO}_2}$ ) fell in response to 1,000 ng ⋅ kg⁻¹ ⋅ min⁻¹infusions 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, pH_a,${\text{Pa}}_{{CO}_2}$ , 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, pH_a,${\text{Pa}}_{{CO}_2}$ , 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.