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 (P_T) to right atrial injections of the thromboxane A₂ (TXA₂) stable analogue STA₂ (0.3, 1.0, and 3.0 μg/kg) before and after administration of atropine sulfate (1 mg/kg), isoprenaline (200 μg/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 P_T. The excitatory responses of RAR activity to STA₂ (0.3–3.0 μg/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 μg/kg), and their combination on P_T in rabbits associated with both artificial ventilation and bilateral vagotomy. The vagally mediated bronchoconstriction that led to an increase in P_T was not enhanced by simultaneous administration of STA₂ at 3.0 μg/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 P_T.