{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:33:37Z","timestamp":1778859217906,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"\n Abstract<\/jats:title>\n \n We investigated second\u2010messenger signalling components linked to the stimulation of G\n q<\/jats:sub>\n protein\u2010coupled receptors (e.g. thromboxane A\n 2<\/jats:sub>\n and bradykinin B2 receptors) on the sensory endings of thin fibre muscle afferents in the chronic mechanoreflex sensitization in rats with myocardial infarction\u2010induced heart failure with reduced ejection fraction (HF\u2010rEF). We hypothesized that injection of either the inositol 1,4,5\u2010trisphosphate (IP\n 3<\/jats:sub>\n ) receptor antagonist xestospongin C (5\u00a0\u00b5g) or the PKC\u03b5 translocation inhibitor PKCe141 (45\u00a0\u00b5g) into the arterial supply of the hindlimb would reduce the increase in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) evoked during 30\u00a0s of 1\u00a0Hz dynamic hindlimb muscle stretch in decerebrate, unanaesthetized HF\u2010rEF rats but not sham\u2010operated controls (SHAM). Ejection fraction was significantly reduced in HF\u2010rEF (45 (19)%) compared to SHAM (80 (9)%;\n P<\/jats:italic>\n \u00a0<\u00a00.001) rats. In HF\u2010rEF rats (\n n\u00a0=\u00a0<\/jats:italic>\n 3M\/2F), IP\n 3<\/jats:sub>\n receptor blockade had no effect on the peak \u0394RSNA (pre: 99 (74)%; post: 133 (79)%;\n P<\/jats:italic>\n \u00a0=\u00a00.974) or peak \u0394MAP response to stretch (peak \u0394MAP: pre: 32 (14) mmHg; post: 36 (21) mmHg;\n P<\/jats:italic>\n \u00a0=\u00a00.719). Conversely, in another group of HF\u2010rEF rats (\n n\u00a0=\u00a0<\/jats:italic>\n 4M\/3F), the PKC\u03b5 translocation inhibitor reduced the peak \u0394RSNA (pre: 110 (77)%; post: 62 (58)%;\n P<\/jats:italic>\n \u00a0=\u00a00.029) and peak \u0394MAP response to stretch (pre: 30 (20) mmHg; post: 17 (16) mmHg;\n P<\/jats:italic>\n \u00a0=\u00a00.048). In SHAM counterparts, neither drug affected the mechanoreflex responses. Our findings highlight PKC\u03b5, but not IP\n 3<\/jats:sub>\n receptors, as a significant second\u2010messenger in the chronic mechanoreflex sensitization in HF\u2010rEF which may play a crucial role in the exaggerated sympathetic response to exercise in this patient population.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Skeletal muscle contraction results in an exaggerated reflex increase in sympathetic nerve activity in heart failure patients with reduced ejection fraction (HF\u2010rEF) compared to healthy individuals, contributing to increased cardiovascular risk and impaired tolerance for mild exercise.<\/jats:p>\n <\/jats:list-item>\n \n \n The exaggerated reflex sympathetic responses in HF\u2010rEF may be attributed to a chronic sensitization of mechanically sensitive thin fibre muscle afferents mediated, at least in part, by stimulation of Gq protein\u2010coupled thromboxane A\n 2<\/jats:sub>\n and bradykinin B2 receptors on muscle afferent sensory endings.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The specific Gq protein\u2010linked signalling mechanisms that produce the chronic mechanoreflex sensitization in HF\u2010rEF have not been investigated but may involve inositol 1,4,5\u2010trisphosphate (IP\n 3<\/jats:sub>\n ) receptors and\/or protein kinase C epsilon (PKC\u03b5).\n <\/jats:p>\n <\/jats:list-item>\n \n \n Here we demonstrate that PKC\u03b5, but not IP\n 3<\/jats:sub>\n receptors, within the sensory endings of thin fibre muscle afferents plays a role in the sensitization of mechanically sensitive thin fibre muscle afferents in rats with HF\u2010rEF.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp287020","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T12:42:14Z","timestamp":1726231334000},"page":"5071-5089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein kinase C epsilon contributes to chronic mechanoreflex sensitization in rats with heart failure"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-5018","authenticated-orcid":false,"given":"Alec L. 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