Effects of thromboxane A2 agonist STA2 on rapidly adapting pulmonary stretch receptors in vagotomized rabbits.

Abstract

We investigated the responses of rapidly adapting pulmonary stretch receptors (RARs) and tracheal pressure (PT) to right atrial injections of the thromboxane A2 (TXA2) stable analogue STA2 (0.3, 1.0, and 3.0 microgram/kg) before and after administration of atropine sulfate (1 mg/kg), isoprenaline (200 micrograms/kg), indomethacin (1 mg/kg), or S-145 (0.5 mg/kg) in artificially ventilated, bilaterally vagotomized rabbits. The RARs increased their activity after STA2 administration, and the increase was dose-dependent. However, intraatrial injections of STA2 at all the doses examined had no significant effect on PT. The excitatory responses of RAR activity to STA2 (0.3-3.0 micrograms/kg) were not significantly altered by administration of atropine sulfate (anticholinergic agent), isoprenaline (bronchodilator), or indomethacin (cyclooxygenase inhibitor). However, S-145 treatment (TXA2 antagonist) blocked the STA2-induced RAR stimulation. To determine whether or not administration of STA2 causes release of acetylcholine (ACh), we also examined the effects of vagal efferent stimulation (10-15 V, 10 Hz, 1 ms), STA2 administration (3.0 micrograms/kg), and their combination on PT in rabbits associated with both artificial ventilation and bilateral vagotomy. The vagally mediated bronchoconstriction that led to an increase in PT was not enhanced by simultaneous administration of STA2 at 3.0 micrograms/kg in all of the tested animals. These results suggest that the stimulation of RARs by STA2 is not mediated by the release of ACh from the nerve endings but is probably due to a local inflammatory bronchoconstriction that does not significantly alter the value of PT.