The thromboxane A2 mimetic U-46619 inhibits somatomotor activity via a vagal reflex from the lung

Abstract

Vagal reflexes from the heart and lungs elicit autonomic as well as somatomotor responses. The purpose of the present investigation was to determine whether the inflammatory mediator thromboxane A2 inhibits the knee-jerk reflex via a vagally mediated reflex from either the heart or the lung. The thromboxane A2 mimetic U-46619 (0.8 ± 0.08 μg/kg) was injected through a catheter placed near the right atrium ( n = 11), near the aortic arch ( n = 7), or into the pericardial sac ( n = 4) in 11 chloralose-anesthetized cats. The knee-jerk reflex, elicited by striking the patellar tendon with a solenoid-driven hammer, was used to evaluate somatomotor activity. The mean maximum tension produced by the knee-jerk reflex was 306 ± 21 g (range 154–471 g). Intravenous U-46619 injection inhibited the knee-jerk reflex by 25 ± 6% and increased peak systolic pressure 53 ± 7 mmHg on average. Bilateral cervical vagotomy abolished the somatomotor inhibition but did not reduce the pressor response. Intra-arterial U-46619 injection inhibited the knee-jerk reflex in two of seven cats and increased peak systolic pressure by 41 ± 11 mmHg. Vagotomy abolished the inhibition in one of the two cats but did not reduce the pressor response. Intrapericardial U-46619 injection did not affect the knee-jerk reflex nor blood pressure. The results indicate that U-46619 inhibited the knee-jerk reflex via a vagal reflex from the lung because the inhibition predominated after intravenous injection and was abolished by vagotomy. Speculation is made that the inflammatory mediator thromboxane A2 may contribute via a vagal reflex to the depression of motor activity associated with sickness behavior.