Blunted pressor and cardioaccelerator responses to electrical stimulation of skeletal muscle afferent nerves in male rats with sporadic Alzheimer’s disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder leading to not only cognitive decline but also impaired somatosensory perception. Stimulation of skeletal muscle afferent fibers during muscle contraction increases blood pressure, known as the exercise pressor reflex (EPR). However, to date, it has not been elucidated whether AD alters the signal transduction associated with the EPR or whether AD alters cardiovascular responses to activation of muscle afferents. We hypothesized that EPR function is indeed altered in AD. Purpose: The aim of this investigation was to determine the cardiovascular responses to stimulation of muscle afferents in a rat model of sporadic AD. METHOD: To generate an sporadic AD rat model, streptozotocin (STZ, 3 mg/kg) was intracerebroventricularly injected into the lateral ventricle of male Sprague–Dawley rats (ICV-STZ, body weight (BW): 385 ± 31 g, n = 17). In parallel, a separate group of rats were treated with ICV saline as a vehicle control (CON, BW: 407 ± 44 g, n = 14). Spatial learning and memory function were assessed using the Morris Water Maze (MWM) behavioral test. During the MWM navigation test (multiple trials over a 4-day period), each rat was placed in a circular pool, and the time to reach a translucent platform recorded. In separate trials, mean arterial pressure (MAP) and heart rate (HR) responses to (1) 30-s passive stretch of the hindlimb muscle, (2) intra-arterial administration of capsaicin (0.3 µg/100 µL), and (3) tibial nerve stimulation at 10 x motor threshold (MT) and at 50 x MT were evaluated. All experiments were performed ten weeks after the administration of the test solution. Results: In the MWM test, the time to reach the platform was progressively shorter over the 4 days of testing in both groups (P < 0.001). As expected, ICV-STZ rats had a significantly longer time to reach the platform as compared to CON rats (P = 0.0046). Peak changes in MAP, HR, and developed tension in response to passive stretch were not different between CON and ICV-STZ rats. Similarly, the peak cardiovascular responses to stimulation by intra-arterial capsaicin injection did not change among groups. However, the peak pressor and cardioaccelerator responses to tibial nerve stimulation at both 10 x MT and 50 x MT were significantly suppressed in ICV-STZ rats compared to CON rats (main effect of group: ΔMAP: P = 0.0003, ΔHR: P = 0.0035; main effect of MT: ΔMAP: P = 0.0111, ΔHR: P = 0.2485). Conclusion: The findings suggest that in experimentally induced sporadic AD, decreased spatial learning and memory function is likewise accompanied by blunted cardiovascular responses to electrical, but not mechanical or chemical, stimulation of muscle afferents. Supported by NIH HL-151632 This abstract was presented at the American Physiology Summit 2025 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.