Abstract 1602: Local Prostaglandins Synthesis Blockade Attenuates the Muscle Sympathetic Nerve Activity Responses to Exercise
Introduction - Animal studies suggest that prostaglandins sensitize mechanically sensitive afferents contributing to the exercise pressor reflex (EPR). However, human data regarding a role for prostaglandins in the EPR are different to interpret and the results are varied; in part because of systemic effects of pharmacologic agents used to block prostaglandin synthesis.
Hypothesis - Local blockade of prostaglandin synthesis in exercising muscles can attenuate the EPR and muscle sympathetic nerve activity (MSNA) responses to forearm exercise.
Method - Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 8 young healthy subjects during static handgrip and post exercise muscle ischemia (PEMI). Local prostaglandins synthesis blockade was accomplished by local infusion of 6 mg ketorolac tromethamine in 50 ml saline into the exercising forearm via Bier block (regional intravenous anesthesia). To separate the effects of ketorolac from the Bier block itself, the same saline was infused via the Bier block (second experiment, N=7). The exercise protocol was performed before and after Bier block in both visits.
Results - Ketorolac Bier block decreased the prostaglandins synthesis to ~26% of the baseline. During the last 30 sec of handgrip before fatigue, MSNA in all 4 conditions increased significantly from the baseline (change from baseline, before ketorolac: Δ22.9±3.6; post ketorolac: Δ16.9±3.7; before saline: Δ21.7±4.0; post saline: Δ28.9±3.0 bursts/min). The increase in MSNA with handgrip after ketorolac was less than that after the saline (P<0.01, 2-way ANOVA). However, there was no significant difference in MSNA responses to PEMI between ketorolac and saline control conditions (before ketorolac: Δ16.5±2.9; post ketorolac: Δ14.2±3.2; before saline: Δ16.1±3.1; post saline: Δ18.9±3.3 bursts/min).
Conclusion - The observations suggest that blockade of prostaglandin synthesis attenuates the mechanoreflex contribution to MSNA seen with the EPR.