Thromboxane A2 acts at a site perfused by the carotid vasculature to mediate cardiovascular and adrenocortical responses.
Increases in thromboxane A2 (TxA2) synthesis are associated with hemodynamic responses and activation of the hypothalamus-pituitary-adrenal axis. This study tested the hypothesis that TxA2 acts on a site perfused by the carotid vasculature to mediate these responses. The TxA2 mimetic U46619 was infused for 30 min into the carotid artery or the vena cava of chronically instrumented adult sheep at doses of 0, 0.25, 0.5, and 1.0 microgram.kg-1.min-1. Mean arterial pressure increased in response to carotid or vena cava U46619 infusions of 0.5 and 1.0 microgram.kg-1.min-1. Heart rate was elevated in response to carotid (0.5 and 1.0 microgram.kg-1.min-1) or vena cava (1.0 microgram.kg-1.min-1) infusions of U46619. Paco2 declined and pH2 increased significantly in response to carotid infusions of 0.5 and 1.0 microgram.kg-1.min-1 but did not change in response to vena cava infusions. Adrenocorticotropic hormone (ACTH) increased in response to carotid infusions of 0.5 microgram.kg-1.min-1, while cortisol increased in response to infusions of 0.25, 0.5, and 1.0 microgram.kg-1.min-1. ACTH and cortisol did not change in response to vena cava infusions. Pao2, hematocrit, and arginine vasopressin did not change significantly. Pulmonary artery pressure and total peripheral resistance increased while cardiac output decreased in response to carotid or vena cava U46619 infusions of 1 microgram.kg-1.min-1; carotid and vena cava responses were not different from one another. We conclude that increases in blood pressure are mediated by peripheral PGH2/TxA2 receptor activation and that pituitary adrenal, blood gas, and heart rate responses are mediated by PGH2/TxA2 receptor activation at a site perfused by the carotid vasculature.
Cudd
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TA
Department of Physiology, University of Florida, Gainesville 32610-0274, USA.
Castellon
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Purinton
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000302:Adrenal Cortex / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002339:Carotid Arteries; D005260:Female; D007261:Infusions, Intra-Arterial; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014682:Vena Cava, Inferior
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000324:Adrenocorticotropic Hormone