Facilitatory Interactions between 5‐HT and Thromboxane A2 in Stimulation of Ischemically Sensitive Cardiac Sympathetic Afferents

We have demonstrated that the endogenously produced mediators serotonin (5‐HT) and thromboxane A 2 (TxA 2 ) contribute to activation of cardiac afferents during ischemia. In the present study we hypothesized facilitatory interactions between these two metabolites in stimulation of cardiac afferents during ischemia. Nerve activity of single cardiac afferent units was recorded from the left sympathetic chain or rami communicantes (T 2 ‐ T 5 ) of anesthetized cats. Twenty ischemically sensitive afferents (CV= 0.28 ‐ 3.62 m/s, 4 Ad‐ and 16 C‐fibers) were identified. We observed that a repeat injection of 5‐HT (40 μg/kg) into left atrium (LA), 4 min after LA 2.5 μg of U46619, a TxA 2 mimetic, induced a significantly larger cardiac afferent response than the first 5‐HT response (0.46±0.08 to 1.06±0.11 vs.0.45±0.13 to 1.90±0.18 imp/s, first vs. second injection, n=3). In a control group, repeated 5‐HT (40 μg/kg, LA) evoked consistent responses in three other ischemically sensitive afferents. Furthermore, LA administration of 5‐HT (40 μg/kg) and U46619 (2.5 μg) caused a larger response than simple addition of the individual responses (n=5). Additionally, the responses of three cardiac afferents to repeat U46619 (2.5 μg, LA) were enhanced compared with the U46619 response before 5‐HT, while the responses of three other cardiac afferents to repeated U46619 stimulation were consistent. Finally, blockade of the 5‐HT 3 receptors with tropisetron (200 μg/kg, iv) attenuated the responses of three cardiac afferent to U46619 (2.5 μg, LA) by 52%. These preliminary data suggest that 5‐HT and TxA 2 each facilitate the responses of ischemically sensitive cardiac afferent endings to the actions of other metabolite (Supported by NIH HL66217).