Contribution of ASIC3 in evoking the mechanoreflex via tendon stretch and intermittent muscle contraction in type 1 diabetic mellitus rats

Previous studies have demonstrated that the exercise pressor reflex, particularly its mechanical component known as the mechanoreflex, is exaggerated in type 1 diabetes mellitus (T1DM). Hypersensitivity to mechanical sensation is also common in T1DM, and acid sensing ion channel 3 (ASIC3) is thought to play a role in evoking this abnormal mechanosensation. It is not known, however, whether ASIC3 also contributes to the exaggerated mechanoreflex observed in T1DM. For this study, we hypothesized that functional knock out (KO) of ASIC3 would normalize the exaggerated mechanoreflex evoked by tendon stretch and intermittent muscle contraction in T1DM rats. To determine this, we used adult, male and female Wistar-Kyoto ASIC3 KO T1DM (n=11; body weight: 341± 37g, glucose: 485 ± 45 mg/dL), ASIC3 KO healthy (n=22; body weight: 364 ± 44 g, glucose: 109 ± 11 mg/dL), wild type (WT) T1DM (n=16; body weight: 304 ± 36 g, glucose: 501 ± 80 mg/dL), and WT healthy (n=20; body weight: 336 ± 22 g, glucose: 109 ± 17 mg/dL) rats. Streptozotocin (50 mg/kg) was injected into fasted, anesthetized rats to induce T1DM, and a random blood glucose >300 mg/dL was used to diagnose diabetes. One week later, the exercise pressor reflex was evoked in unanesthetized, decerebrated rats via 30 s tendon stretch or 30 s intermittent muscle contraction. Peak changes (Δ) in mean arterial pressure (MAP) and heart rate (HR) were calculated. One-way ANOVA with Holm-Sidak post hoc was used to compare means between groups, with significance set at P< 0.05. Contrary to our hypothesis, no significant differences were observed in peak pressor or cardioaccelerator responses to tendon stretch between KO T1DM and WT T1DM rats (Δ MAP KO T1DM: 20 ± 8 mmHg, n=11 vs. WT T1DM: 20 ± 7 mmHg, n=16, P >0.99; ΔHR KO T1DM: 13 ± 8 bpm vs. WT T1DM: 15 ±11 bpm, P=0.97). However, peak pressor and cardioaccelerator responses to intermittent contraction were significantly lower in KO T1DM compared with WT T1DM (ΔMAP KO T1DM: 13 ± 6 mmHg, n=10 vs. WT T1DM: 22 ± 8 mmHg, n=13 P=0.005; ΔHR KO T1DM: 12 ± 7 bpm vs. WT T1DM: 21 ± 11 bpm; P=0.02). These responses to intermittent contraction were similar between KO healthy and WT healthy (ΔMAP KO healthy: 14 ± 5 mmHg, n=15 vs. WT healthy: 15 ± 6 mmHg, n=14 P >0.99; ΔHR KO healthy: 11 ± 6 bpm vs. WT healthy: 13 ± 7 bpm; P=0.96). Developed tensions for tendon stretch and intermittent contraction were similar for each comparison, P >0.05 for all. Our findings suggest that ASIC3 does not play a significant role in evoking the mechanoreflex in T1DM; however, it does play a role in evoking the exaggerated exercise pressor reflex in T1DM, but not healthy, rats during intermittent muscle contraction. This project was supported by NIH R01HL 166323. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.