title: Thromboxane A(2) mimetic evokes a bradycardia mediated by stimulation of cardiac vagal afferent nerves.
abstract: Injections of the thromboxane A(2) mimetic U-46619 (10 and 20 microg) into the left atrium of anesthetized rabbits evoked decreases in heart rate (HR) and arterial blood pressure (ABP) followed by an increase in ABP. Bilateral, cervical vagotomy abolished the U-46619-induced bradycardia and attenuated the hypotension. Injections of U-46619 into the ascending aorta did not evoke the bradycardia and hypotension but did cause arterial hypertension. To further define the origin of the vagal reflex, recordings of nerve impulses were made from 11 chemosensitive cardiac vagal afferent nerves. Impulse frequency increased in all 11 fibers in response to left atrial injections of phenylbiguanide (20-30 microg) and U-46619 (5-10 microg). Onset time of nerve activity induced by U-46619 correlated with the onset time of bradycardia. We conclude that U-46619 injections into the left heart elicit decreases in HR and ABP via a vagal reflex that originates from the heart similar to the coronary chemoreflex described for other agents.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wacker
authors.forename: Roya N
authors.initials: RN
authors.lastname: Tehrani
authors.forename: Rory L
authors.initials: RL
authors.lastname: Smoot
authors.forename: James A
authors.initials: JA
authors.lastname: Orr
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D002628:Chemoreceptor Cells / Q000502:physiology; D005260:Female; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives*; D014628:Vagotomy; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D001645:Biguanides; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C008846:phenyl biguanide