Effects of Direct Afferent Nerve Stimulation Frequency and Intensity In Evoking the Exercise Pressor Reflex
Authors: Harms Jonathan E , Copp Steven J , Kim Joyce M , Kaufman Marc P 
Published: November 2023

Contraction of freely perfused hind limb muscles in decerebrate rats evokes the exercise pressor reflex, resulting in sympathetic activation and increased blood pressure. This reflex is primarily propagated along mechanically sensitive group III and metabolically sensitive group IV afferent nerve fibers. Recent research by our laboratory has focused on the exaggeration of the exercise pressor reflex in decerebrate rats with simulated peripheral artery disease, which was induced by ligating the femoral artery for 72 hours before the start of the experiment. Recently, we showed that ligating the femoral artery increased the responses of single fiber group III and IV triceps surae muscle afferents to static contraction. The objective of the present study was to determine if electrical stimulation of group III and IV afferents at frequencies approximating those occurring during static contraction was capable of reflexively increasing arterial blood pressure.

In decerebrate unanesthetized rats, we first determined motor threshold by gradually increasing the current applied as a single pulse (0.01 ms) to the gastrocnemius nerve until a twitch was evoked from the triceps surae muscles. Once motor threshold was determined, we injected intravenously pancuronium bromide to paralyze the rat for the remainder of the experiment. Five minutes later, we stimulated the sciatic nerve for 30 seconds at either 5, 20, or 100 times motor threshold, currents that presumably recruited thick group III, thick and thin group III, and all group III and IV fibers, respectively. In addition, we stimulated (0.01 ms pulse duration) the gastrocnemius nerves with six different frequencies (0.1, 0.25, 0.5, 1.0, 3.0, or 5.0 Hz), applying them in random order. Particular attention was paid to frequencies of 0.25, 0.5 and 1.0 Hz because these represented the discharge rates displayed by group III and IV afferents responding to static contraction.

Overall, we found that stimulation of the gastrocnemius nerve increased arterial blood pressure in a graded fashion as both stimulus frequency and motor threshold were increased. In particular, stimulation of the gastrocnemius nerve at 100 times motor threshold (n=7) significantly increased arterial blood pressure (MAP) over baseline levels at 0.25 Hz (Peak ΔMAP= 11 ± 2 mmHg, p< 0.001), 0.5 Hz (Peak ΔMAP= 13 ± 3 mmHg, p< 0.01), and 1.0 Hz (Peak ΔMAP= 18 ± 4 mmHg, p< 0.01).

In conclusion, we observed that afferent stimulation frequencies as low as 0.25 Hz are sufficient to increase arterial blood pressure. These findings are relevant, as previous studies from our lab have measured afferent responses to contraction in these frequency ranges. Additionally, we observed that increasing stimulus frequency resulted in greater increases in blood pressure, a finding that parallels our previous results in studies using ligated rats. As such, these and future studies provide valuable insight into the mechanisms underlying the exaggerated exercise pressor reflex we observe in an animal model of peripheral artery disease.

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Funded by NIH R01 ‐ AR059397