Thromboxane A2 does not act at the carotid sinus to mediate cardiovascular, adrenocorticotropin, cortisol, or blood gas responses

Thromboxane A2 (TxA2), well known as a vasoconstrictor and activator of platelets, also stimulates reflex cardiovascular, pituitary, adrenocortical, and blood gas responses, although the site of action is unknown. Previously we determined that the site of these actions is perfused by the carotid vasculature. The purpose of the present study was to test the hypothesis that TxA2 stimulates these responses by acting at the carotid sinus. The TxA2 mimetic U46619 (1 microgram.kg-1.min-1) or saline was infused into the carotid artery (CA) or vena cava in conscious, chronically instrumented carotid sinus denervated (CSD) or sham-operated sheep. Mean arterial pressure increased in all groups receiving U46619. Heart rate increased only in the CSD group receiving CA infusions of U46619. Adrenocorticotropic hormone (ACTH) and cortisol increased in the sham and CSD groups receiving CA U46619, and responses were not different between sham and CSD groups. PaCO2 values were higher in all CSD treatment groups compared with sham treatment groups. Arterial pH increased and PaCO2 decreased in both the sham and CSD groups in response to CA U46619. Although PaCO2 values were higher overall in the CSD group, the magnitude of change in response to U46619 infusions was similar in sham and CSD animals. There was no difference in pHa between CSD and sham groups. Hematocrit and PaO2 did not change. We conclude that TxA2 does not act at the carotid sinus, as responses to U46619 infusions in CSD animals were not different in the cases of ACTH, cortisol, and blood gases, or were enhanced rather than diminished in the case of heart rate. These findings support a hypothesis that TxA2 acts at the brain to mediate cardiovascular, pituitary, adrenocortical, and blood gas responses.