Effects of the thromboxane A2 mimetic, U46,619, on pulmonary vagal afferents in the cat

Abstract

Release of thromboxane A₂ (TxA₂) or infusion of the TxA₂ mimetic U46,619 in the cat elicits pulmonary hypertension and rapid shallow breathing (Shams et al., Respir. Physiol. 71: 169–183, 1988). The vagus nerve mediates the observed respiratory, but not the circulatory, effects (Shams and Scheid, J. Appl. Physiol. 68: 2042–2046, 1990). To identify the type of lung vagal afferent fibers involved in this respiratory response to TxA₂, we have recorded the functional single-unit activity and its response to infusion of U46,619 in fine strands of the vagus nerve in the artificially ventilated cat and rabbit. The fibers were classified as originating from slowly adapting (SAR) or rapidly adapting (RAR) stretch receptors by their response to sustained pulmonary inflation (intrapulmonary pressure of 20–25 cmH₂O) or as C-fibers, by their response to a bolus injection of phenylbiguanide. C-fibers responded variably to lung inflation. U46,619 infusion caused only a small increase in SAR or RAR activity along with increases in end-inspiratory tracheal airway pressure (Paw), but evoked a marked increase in the firing rate of C-fibers, independent of their response to lung inflation. This increase in C-fiber activity was unrelated to the increase in Paw, which accompanied the infusion of U46,619. Since these responses remained the same after indomethacin they appear to be due to a direct action of U46,619, and not to be mediated by prostanoids that might be released by U46,619.

These data suggest that C-fibers are indeed involved in the respiratory effects of TxA₂. Since the effects exerted on C-fibers by U46,619 were unrelated to increased Paw, TxA₂ is likely to stimulate the nerve endings directly, rather than via smooth muscle contraction. On the other hand, the small stimulating effect of U46,619 on SAR and RAR may be mediated by bronchoconstriction.