The role of the cyclooxygenase products in evoking sympathetic activation in exercise

Abstract

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment (n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to approximately 33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Delta502 +/- 111; post ketorolac: Delta348 +/- 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block (P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.

Figure 1

Effects of ketorolac on thromboxane B₂ levels. Panel A: before and after Keto Bier Block. Panel B: before and after saline Bier Block. The thromboxane B₂ levels are expressed in arbitrary units by assigning the control baseline a value of 100. Subject number = 12. *: P<0.05 vs. the respective prior exercise baseline. †: P<0.05 vs. the respective control trial condition.

Figure 2

Representative tracing of handgrip force, heart rate, muscle sympathetic nerve activity (MSNA) and arterial blood pressure (BP) during the last period of handgrip and post exercise ischemia (PEMI). Panel A: before Ketorolac Bier block. Panel B: after Ketorolac Bier block. FHG: the last 30 sec of handgrip before fatigue.

Figure 3

MSNA and cardiovascular responses during the fatiguing handgrip exercise before and after local administration of ketorolac or saline into the exercising arm via Bier block procedure. The values are changes from the prior exercise baseline. The responses were during the last 30 sec handgrip before fatigue (see Figure 2). ΔMSNA% shows the total activity of MSNA response. The MSNA, heart rate (HR) and MAP during the fatiguing handgrip in all 4 trials were significantly greater than the rest baselines (all P<0.001). *: P<0.05 vs. respective control trial. †: P<0.05 vs. Ketorolac Bier block trial.

Figure 4

MSNA and cardiovascular response to post exercise muscle ischemia (PEMI) after fatiguing handgrip before and after local administration of ketorolac or saline into the exercising arm via Bier block procedure. The data over the last 2 min of 2.5 min PEMI were analyzed. The values are changes from the prior exercise baseline. ΔMSNA% shows the total activity of MSNA response. The MSNA and MAP during the PEMI in all 4 trials were significantly greater than the rest baselines (all P<0.001). *: P<0.05 vs. respective control trial.