Thromboxane A2 mimetic, U46,619, and slowly adapting stretch receptor activity in the rabbit

The effect of infusing the thromboxane A2 mimetic U46,619 on afferent activity from slowly adapting airway stretch receptors (SARs) in the anesthetized rabbit was examined in these experiments. SAR vagal afferent fibers (n = 29) were identified by their slow adaptation to a sustained (10-15 s duration) lung inflation in the closed-chest, mechanically ventilated animal (n = 16). Intravenous infusion of U46,619 increased the discharge frequency of the SAR, measured at the end of inspiration, in a dose-dependent manner: by 6.6% and 8.0% at doses of 0.1 and 0.5 microgram of U46,619/kg, respectively. This increase in SAR activity was correlated with increases in end-inspiratory tracheal airway pressure (6.4% at 0.1 micrograms/kg and 9.1% at 0.5 micrograms/kg). Higher doses of U46,619 could not be administered due to decreases in systemic arterial blood pressure. The increase in SAR activity and tracheal airway pressure was qualitatively comparable to the response to histamine (25 micrograms/kg), a known bronchoconstrictor. We conclude that intravenous infusion of U46,619 in the anesthetized rabbit at doses that elicit significant hemodynamic effects causes modest bronchoconstriction and comparable increases (less than 10%) in SAR afferent nerve activity. From these data, it appears that U46,619 has no direct effect on SARs, but rather increases SAR activity due to bronchoconstriction.