Thromboxane A2 mimetic U-46619 induces systemic and pulmonary hypertension and delayed tachypnea in the goat.
Cardiorespiratory variables were measured continuously in five conscious goats before and after the infusion of U-46619 at a dose of either 2, 4, or 6 micrograms.kg-1.5 min-1. Infusion of U-46619 led to immediate increases in pulmonary arterial blood pressure (ABP) that were sustained for up to 15 min after the end of the infusion. Systemic ABP also increased, but the relative increase from control was less than the pulmonary pressor response. At the highest dose, U-46619 elicited a delayed tachypneic response that was greatest several minutes after the infusion was stopped. U-46619 was also infused simultaneously with sodium nitroprusside to clamp ABP pressure at baseline levels to determine whether stimulation of baroreceptors might contribute to the latency of the tachypneic response. Although sodium nitroprusside infusion prevented the increase in ABP, the increase in breathing frequency was still delayed 3-4 min from the start of the infusion. We conclude that U-46619 elicits pulmonary and systemic arterial hypertension in the conscious goat. At the higher dose U-46619 also elicits a delayed tachypnea that remains delayed even if ABP is normal.
Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045.
J A
JA
Carrithers
D
D
Brown
F
F
Liu
J A
JA
Orr
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006041:Goats; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000633:toxicity*; D012120:Respiration Disorders / Q000139:chemically induced* / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000633:toxicity; D014662:Vasoconstrictor Agents / Q000633:toxicity*
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D010656:Phenylephrine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid