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To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1<jats:sup>+\/+<\/jats:sup>, TRPV1<jats:sup>+\/\u2212<\/jats:sup> and TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> rats. Carotid arterial injection of capsaicin (0.5\u00a0\u03bcg), evoked significant pressor responses in TRPV1<jats:sup>+\/+<\/jats:sup> and TRPV1<jats:sup>+\/\u2212<\/jats:sup> rats, but not in TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1<jats:sup>+\/+<\/jats:sup> and TRPV1<jats:sup>+\/\u2212<\/jats:sup> rats but not in neurons isolated from TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1<jats:sup>+\/+<\/jats:sup>, TRPV1<jats:sup>+\/\u2212<\/jats:sup> and TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> rats with patent femoral arteries averaged 17.1 \u00b1 7.2, 18.9 \u00b1 12.4 and 18.4 \u00b1 8.6\u00a0mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid\u2010sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15790-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using genetically engineered rats in which the TRPV1 channel is rendered non\u2010functional, we have shown that it is not needed to evoke the metaboreflex.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285267","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T15:45:04Z","timestamp":1698248704000},"page":"5241-5256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional knockout of the TRPV1 channel has no effect on the exercise pressor reflex in rats"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8558-1155","authenticated-orcid":false,"given":"Laura","family":"Anselmi","sequence":"first","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-4678","authenticated-orcid":false,"given":"Guillaume P.","family":"Ducrocq","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey PA USA"},{"name":"Mitochondria, Oxidative Stress and Muscular Protection Laboratory (UR 3072), Faculty of Medicine University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Ruiz\u2010Velasco","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey PA USA"},{"name":"Department of Anesthesiology and Perioperative Medicine Penn State College of Medicine Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6317-6300","authenticated-orcid":false,"given":"Sean D.","family":"Stocker","sequence":"additional","affiliation":[{"name":"Department of Neurobiology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon P.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61255-1"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00462.2010"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00398.2012"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201704-0769OC"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(90)90237-3"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.6"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009498"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271714"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4482"},{"key":"e_1_2_5_11_1","first-page":"H315","article-title":"Reflex cardiovascular response during injection of capsaicin into skeletal muscle","volume":"240","author":"Crayton S. 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