thromboxane-a2 and Bradycardia

The aim of the current study was to determine the central cyclooxygenase (COX) pathway and central thromboxane signaling in the cardiovascular effects evoked by arachidonic acid (AA). As a main control for the study, different doses of AA (75, 150, or 300 µg) were administered intracerebroventricularly (i.c.v.). Centrally injected AA dose- and time-dependently increased mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. The maximal cardiovascular effects of AA were observed at min 10 of the injection and lasted almost 30 min. To investigate the central mechanism of the AA-induced cardiovascular effect in conscious normotensive animals, pretreatment with nonselective COX inhibitor indomethacin (200 µg; i.c.v.), thromboxane A2 (TXA2) synthesis inhibitor furegrelate (250 or 500 µg; i.c.v.), or TXA2 receptor antagonist SQ-29548 (8 or 16 µg; i.c.v.) was carried out 15 min before AA (150 µg; i.c.v.) injection. While indomethacin completely prevented the pressor and bradycardic responses to AA, furegrelate and SQ-29548 attenuated these effects in part in awake normotensive rats. In conclusion, these findings suggest that the pressor and bradycardic cardiovascular effects of centrally injected AA are dependent on COX activity being totally central and the TXA2 signaling pathway being subsequently central, at least in part.

Topics: Animals; Arachidonic Acid; Benzofurans; Blood Pressure; Bradycardia; Bridged Bicyclo Compounds, Heterocyclic; Cardiovascular System; Fatty Acids, Unsaturated; Heart Rate; Hydrazines; Indomethacin; Infusions, Intraventricular; Male; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane A2, Prostaglandin H2; Signal Transduction; Thromboxane A2

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.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Anesthesia; Animals; Biguanides; Blood Pressure; Bradycardia; Chemoreceptor Cells; Female; Heart Atria; Heart Rate; Hypertension; Hypotension; Male; Neurons, Afferent; Rabbits; Reflex; Serotonin Receptor Agonists; Thromboxane A2; Vagotomy; Vagus Nerve; Vasoconstrictor Agents