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Laura Anselmi, Victor Ruiz-Velasco, Sean D. Stocker, Shannon P. Higgins, Guillaume P. Ducrocq and Marc P. Kaufman. The role played by the transient receptor potential vallinoid-1 (TRPV1) on the endings of thin fiber muscle afferents in evoking the exercise pressor reflex is controversial. To shed light on this controversy, we used TRPV1-/- rats that were made by a CRISPR-Cas9 deletion to introduce a 26-bp frameshift deletion in exon 3. We compared the magnitude of the reflex between TRPV1 +/+ wild-type rats (WT), TRPV1+/- heterozygous rats (HET), and TRPV1-/- knockout rats (KO). The exercise pressor reflex was evoked by stimulating the tibial nerve (40Hz, 0.01ms, 1.5 times motor threshold) in precollicular decerebrated unanesthetized rats whose femoral arteries were either freely perfused or were occluded for 30 sec before the start of contraction. We found that there was no difference between the magnitude of the reflex in the three groups of rats with freely perfused hindlimbs (p=0.61). Specifically, the exercise pressor reflex averaged 16.4 ± 2.2 mmHg in WT rats (n=9), 21.1 ± 5 mmHg in HET rats (n=9), and 17.7 ± 2.3 mmHg in KO rats (n=9). No difference was also observed among the three groups of rats that received acute femoral artery occlusion (p=0.79). Specifically, the peak exercise pressor reflex averaged 15.3 ± 2.2 mmHg in WT rats (n=4), 19.8 ± 4.7 mmHg in HET rats (n=6), and 19 ± 8 mmHg in KO rats (n=3). Stimulation of the tibial nerve after paralysis of the rats with pancuronium (iv) had trivial effects on arterial pressure indicating that the pressor responses to contraction were not caused by electrical stimulation within the axon of the tibial nerve. Intra-carotid arterial injection of the TRPV1 agonist, capsaicin (0.5 mg), evoked a significant pressor response in the WT rats (34.7 ± 9.2 mmHg) and in the HET rats (36.3 ± 7.2 mmHg), but not in the KO rats (3.2 ± 0.4 mmHg). In electrophysiological studies of dorsal root ganglion cells innervating the gastrocnemius muscles, capsaicin evoked inward currents in the WT and HET rats, but not in the KO rats. Moreover, immunofluorescence revealed the presence of TRPV1 in the DRG of WT, but not in the DRG of KO rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex either in rats whose femoral arteries were either freely perfused or were occluded. These results are consistent with our previous finding that pharmacological antagonism of TRPV1 had no effect on the exercise pressor reflex. Supported by HL156594 and HL 156513 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.