Purinergic 2 receptor blockade prevents the responses of group IV afferents to post-contraction circulatory occlusion

Abstract

ATP, by activating purinergic 2 (P2) receptors on group III and IV afferents, is thought to evoke the metabolic component of the exercise pressor reflex. Previously we have shown that injection of PPADS, a P2 receptor antagonist, into the arterial supply of skeletal muscle of decerebrated cats attenuated the responses of group III and IV afferents to static contraction while the muscles were freely perfused. We have now tested the hypothesis that injection of PPADS (10 mg kg(-1)) attenuated the responses of group III (n = 13) and group IV afferents (n = 9) to post-contraction circulatory occlusion. In the present study, we found that PPADS attenuated the group III afferent responses to static contraction during circulatory occlusion (P < 0.05). Likewise, PPADS abolished the group IV afferent responses to static contraction during occlusion (P = 0.001). During a 1 minute period of post-contraction circulatory occlusion, four of the 13 group III afferents and eight of the nine group IV afferents maintained their increased discharge. A Fischer's exact probability test revealed that more group IV afferents than group III afferents were stimulated by post-contraction circulatory occlusion (P < 0.02). In addition, the nine group IV afferents increased their mean discharge rate over baseline levels during the post-contraction circulatory occlusion period, whereas the 13 group III afferents did not (P < 0.05). PPADS abolished this post-contraction increase in discharge by the group IV afferents (P < 0.05). Our findings suggest that P2 receptors on group IV afferents play a role in evoking the metabolic component of the exercise pressor reflex.

Figure 1. Summary of responses of 13 group III afferents to static contraction while the triceps surae muscles were freely perfused (A) and while their circulation was occluded (B)

A, discharge rates of group III afferents responding to static contraction while the circulation to the muscles was freely perfused, both before (Pre) and after (Post) PPADS was injected into the popliteal artery (10 mg kg⁻¹). B, discharge rates of group III afferents responding to static contraction while the circulation to the muscles was occluded, both before (Pre) and after (Post) PPADS was injected into the popliteal artery (10 mg kg⁻¹). Filled bars represent baseline means (base) and open bars represent means during contraction (peak). Hatched bars represent the mean discharge rate during a 1 min period of post-contraction circulatory occlusion (PCO). Vertical brackets represent standard errors. Asterisks represent a significant difference (P < 0.05) between baseline and either contraction or PCO. Horizontal brackets represent a significant difference (P < 0.05) between the increase in discharge due to contraction before and after PPADS.

Figure 2. Summary of responses of nine group IV afferents to static contraction while the triceps surae muscles were freely perfused (A) and while their circulation was occluded (B)

A, discharge rates of group IV afferents responding to static contraction while the circulation to the muscles was freely perfused, both before (Pre) and after (Post) PPADS was injected into the popliteal artery (10 mg kg⁻¹). B, discharge rates of group IV afferents responding to static contraction while the circulation to the muscles was occluded, both before (Pre) and after (Post) PPADS was injected into the popliteal artery (10 mg kg⁻¹). Filled bars represent baseline means (base) and open bars represent means during contraction (peak). Hatched bars represent the mean discharge rate during a 1 min period of post-contraction circulatory occlusion (PCO). Vertical brackets represent standard errors. Asterisks represent a significant difference (P < 0.05) between baseline and either contraction or PCO. Horizontal brackets represent a significant difference (P < 0.05) between the increase in discharge due to contraction before and after PPADS, and a significant difference (P < 0.05) in discharge due to PCO before and after PPADS.

Figure 3. Responses of a single group IV afferent (conduction velocity = 1.7 m s⁻¹) to static contraction while while the triceps surae muscles were freely perfused (A and B) and while their circulation was occluded (C and D) both before (Pre PPADS; A and C) and after (Post PPADS; B and D) PPADS, which was injected into the popliteal artery (10 mg kg⁻¹)

Static contraction started at time zero and lasted for 60 s (filled horizontal bar). Circulatory occlusion was started 3 min prior to contraction and maintained during and 1 min after contraction (open horizontal bar). Only the 60 s immediately prior to contraction is shown. Insets show the recording of the action potential, as denoted by the arrow. Horizontal bar in inset represents 280 ms. Abbreviation: TTI, tension time index. Stars identify action potentials discharged by group IV afferent.