Changes in cardiac function mediated by thromboxane A(2)

Thromboxane A₂ (TXA₂) is released during tissue trauma and induces platelet aggregation and vascular smooth muscle contraction. More recent work has shown that TXA₂ stimulates peripheral nerves from the lung and skeletal muscle. This study extends the actions of TXA ₂ to the heart. Left atrial injections of the TXA₂ mimetic, U-46619, stimulated cardiac vagal sensory nerves and elicited decreases in heart rate (HR) and arterial blood pressure (ABP) in the anesthetized rabbit. Subsequent experiments revealed that a significant contributor to the U-46619-induced coronary chemoreflex was the release of serotonin (5-HT) and subsequent activation of the 5-HT₃ receptor.; It is also possible that the TXA₂ receptor (TP) is located on vagal afferent nerve endings and plays a role in vagal responses to TXA ₂. In preparation for this investigation, oligonucleotide primers were designed to detect mRNA for the rabbit TP receptor using standard PCR and RT-PCR procedures. PCR products of the putative rabbit TP receptor gene were then cloned and sequenced. Preliminary data using single cell RT-PCR revealed TP receptor expression in cultured rabbit nodose ganglion neurons. These results suggest that TXA₂ may be a significant member of the prostanoid family in not only evoking the release of agents which stimulate peripheral nerves but may also participate in the stimulation or sensitization of nerves via a direct receptor mediated event at the sensory ending of the peripheral nerve.; Along with the ability to stimulate peripheral reflexes, it was also observed that left atrial injections of U-46619 (10–30 μg) evoked arrhythmias in the absence of manual coronary artery occlusion. The arrhythmias involved premature QRS complexes of both normal and abnormal morphology. It was observed that bilateral cervical vagotomy increased the number of arrhythmias while β-adrenergic receptor blockade had no effect. The influences of other agents that have similar actions to U-46619 such as phenylephrine and PGF_2α were also investigated and found not to induce arrhythmias. Results from these four series of experiments contribute to the growing list of actions of TXA₂. TXA₂ when released during events such as myocardial ischemia may evoke more complex actions than simply platelet aggregation and vasoconstriction.