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1 Medicine/Cardiology, Penn State Heart & Vascular Institute, Hershey, Pennsylvania, United States
2 Anesthesiology, Pennsylvania State University, Hershey, Pennsylvania, United States
3 Hershey, Pennsylvania, United States; Medicine/Cardiology, Penn State Heart & Vascular Institute, Hershey, Pennsylvania, United States
4 Medicine/Cardiology, Penn State Heart & Vascular Institute, Hershey, Pennsylvania, United States; Hershey, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: lsinoway{at}psu.edu.
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 pharmacologic 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 post exercise muscle ischemia (PEMI) before and after local infusion of 6 mg 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 ~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: 
502±111; post ketorolac: 348±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.
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