Vagal blockade does not prevent adrenocorticotropin, cortisol, and cardiopulmonary responses to thromboxane A(2)

Previously, we reported that thromboxane A(2) (TxA(2)) mediates heart rate, adrenocorticotropin (ACTH), cortisol, and blood gas responses, although th e specific site of action was not identified. In the present study, we inte rrupted vagal nervous transmission in chronically instrumented conscious sh eep and infused the TxA(2) mimetic U46619 or saline into the carotid artery or U46619 into the vena cava to determine whether TxA(2) acts at vagal aff erent nerves. Heart rate increased in all three groups during vagal blockad e, and responses were not different between groups. Carotid artery and intr avenous infusions of U46619 resulted in an increase in blood pressure, but responses were not different between groups. Pao(2) decreased in response t o vagal blockade in all groups, and responses were not different among grou ps. Arterial PH increased and Paco(2) decreased during vagal blockade in re sponse to carotid artery U46619 infusions but not in response to vagal bloc kade alone or combined with carotid artery saline or intravenous U46619. AC TH, cortisol, and hematocrit increased significantly in response to carotid artery infusions of U46619 during vagal blockade but not in response to ca rotid artery saline or intravenous U46619 infusions. In summary, carotid ar tery infusions of TxA(2) mimetic result in ACTH, cortisol, Paco(2), pHa, an d hematocrit responses that are not prevented by vagal blockade. We conclud e that these responses are mediated at a site perfused by the carotid vascu lature and not at a site innervated by the vagal nerves, findings consisten t with the hypothesis that TxA(2) acts on the brain to mediate cardiopulmon ary and pituitary-adrenal responses.