Mechanisms for the tachypneic response to the thromboxane A2 mimetic U-46,619 in rabbits

J. A. Carrithers, F. Liu, H. W. Shirer and J. A. Orr Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045. These experiments were designed to determine if intravenous infusion of the thromboxane A2 mimetic, U-46,619, would elicit tachypnea in the rabbit, and if so whether the afferent signal was generated by receptors innervated by myelinated or unmyelinated vagal nerve fibers. Intravenous infusion of U-46,619 (0.5 microgram/kg delivered over 10 s) increased breathing frequency (26%) and right ventricular blood pressure (59%) in the anesthetized rabbit (n = 10). Systemic arterial blood pressure, heart rate, and tidal volume were unaffected by the infusion of U-46,619. When myelinated fiber conduction in the vagus nerve was eliminated by bilaterally cooling the nerve to 6 degrees C, the increase in breathing frequency was only 5% above baseline levels. The tachypneic response to U-46,619 was totally eliminated when both myelinated and unmyelinated fiber conduction was abolished by cooling the vagi to 0 degree C. The increase in right ventricular blood pressure after U-46,619 infusion was unaffected by vagal cooling. Because most (> 80%) of the tachypneic response to U-46,619 was eliminated by blockade of myelinated vagal fiber conduction, we conclude that the tachypneic response to U-46,619 is mediated mostly by receptors innervated by myelinated vagal afferent fibers in the anesthetized rabbit.