Vagal blockade does not prevent adrenocorticotropin, cortisol, and cardiopulmonary responses to thromboxane A2.
Previously, we reported that thromboxane A2 (TxA2) mediates heart rate, adrenocorticotropin (ACTH), cortisol, and blood gas responses, although the specific site of action was not identified. In the present study, we interrupted vagal nervous transmission in chronically instrumented conscious sheep and infused the TxA2 mimetic U46619 or saline into the carotid artery or U46619 into the vena cava to determine whether TxA2 acts at vagal afferent nerves. Heart rate increased in all three groups during vagal blockade, and responses were not different between groups. Carotid artery and intravenous infusions of U46619 resulted in an increase in blood pressure, but responses were not different between groups. PaO2 decreased in response to vagal blockade in all groups, and responses were not different among groups. Arterial pH increased and PaCO2 decreased during vagal blockade in response to carotid artery U46619 infusions but not in response to vagal blockade alone or combined with carotid artery saline or intravenous U46619. ACTH, cortisol, and hematocrit increased significantly in response to carotid artery infusions of U46619 during vagal blockade but not in response to carotid artery saline or intravenous U46619 infusions. In summary, carotid artery infusions of TxA2 mimetic result in ACTH, cortisol, PaCO2, pHa, and hematocrit responses that are not prevented by vagal blockade. We conclude that these responses are mediated at a site perfused by the carotid vasculature and not at a site innervated by the vagal nerves, findings consistent with the hypothesis that TxA2 acts on the brain to mediate cardiopulmonary and pituitary-adrenal responses.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002319:Cardiovascular System / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000494:pharmacology; D009407:Nerve Block; D010100:Oxygen / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012756:Sheep; D013928:Thromboxane A2 / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*