Reciprocal interactions between bradykinin and thromboxane A2 during stimulation of ischemically sensitive cardiac spinal afferent

Abstract

We have demonstrated that the ischemic metabolites thromboxane A2 (TxA2) and bradykinin (BK) contribute to activation of cardiac afferents during ischemia. The present study tested the hypothesis that there are reciprocal interactions between these two metabolites in stimulation of ischemically sensitive cardiac afferents. Nerve activity of single cardiac afferent units was recorded from the left sympathetic chain or rami communicantes (T2 – T5) of anesthetized cats. Twenty two ischemically sensitive afferents (CV= 0.46 – 4.34 m/s, 5 Aδ17 C‐fibers) were identified. In the first protocol, a repeat injection (2.5 μg) of TxA2 into left atrium (LA) 4 min after administration of BK (1 μg, LA) induced a significantly larger cardiac afferents’ response than the first TxA2 response (0.55±0.17 to 1.54±0.41 vs.0.64±0.13 to 2.28±0.36 imp/s, first vs. second injection, n=5). In a control group, repeated TxA2 (2.5 μg, LA) evoked consistent responses in four other ischemically sensitive afferents. Secondly, we observed that administration of TxA2 (2.5 μg) and BK (1 μg, LA) together appeared to cause a response that was approximately additive of the individual responses. Finally, blockade of the TxA2 receptors with BM13177 attenuated the responses of four cardiac afferent to BK (1 μg, LA) by 47%. In contrast, repeated BK (1 μg, LA) induced a consistent discharge activity in three other afferents. These preliminary data suggest that BK and TxA2 reciprocally enhance the responses of ischemically sensitive cardiac afferent endings to the other metabolite (Supported by NIH HL66217).