An Exaggerated Muscle Mechanoreflex in Type 2 Diabetic Rats Is Mediated by Potentiated Skeletal Muscle Afferent Discharge to Mechanical Stimulation
Authors: Ishizawa Rie , Kim Han Kyul , Hotta Norio , Iwamoto Gary A , Vongpatanasin Wanpen , Mitchell Jere H. , Smith Scott A , Mizuno Masaki 
Published: June 2021

The blood pressure response to exercise is heightened in patients with type 2 diabetes (T2D). Since such elevations in blood pressure increase the risk for developing an adverse cardiovascular event, elucidating the underlying mechanisms is clinically relevant. The exercise pressor reflex (EPR) plays an important role in regulating the cardiovascular system during exercise. Our group has previously demonstrated that the EPR is exaggerated in T2D rats contributing importantly to the augmented pressor response to physical activity. However, the mechanisms responsible for this abnormal EPR function in T2D remain to be elucidated. Sensory information from working muscle is generated, in part, by stimulation of mechanically sensitive afferent neurons (i.e. the skeletal muscle mechanoreflex, a component of the EPR). In this study, it was hypothesized that the EPR dysfunction characteristic of T2D is mediated by an exaggerated muscle mechanoreflex resulting from an increase in muscle afferent responsiveness to mechanical stimulation.PURPOSEIn T2D rats, to 1) investigatethe pressor and sympathetic responses to stimulation of the muscle mechanoreflex in vivo and 2) examine neuronal discharge to mechanical stimulation in skeletal muscle thin fiber afferents in vitro.METHODSFor 14–16 weeks, rats were given either a normal diet (control group) or a high fat diet in combination with a low dose (35 mg/kg) of streptozotocin (T2D group). In vivo, we measured changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) during passive stretch of hindlimb muscle in decerebrate rats. In vitro, muscle afferent neurons were mechanically activated via ramp‐shaped mechanical stimulation (0–196 mN) with the resulting action potentials assessed by obtaining single‐fiber recordings using an extensor digitorum longusmuscle‐nerve preparation.RESULTSCompared to control, induction of T2D evoked hyperglycemia (104±5 vs. 161±10 mg/dL, P<0.05). Similarly, T2D elicited significant increases in plasma insulin (111±10 vs. 150±13 pmol/L, P<0.05) and HOMA‐IR (3.9±0.3 vs. 9.3±1.2, P<0.01). Mechanoreflex activationby passive stretch evoked significantly greater increases in RSNA and MAP in T2D (13±3 vs. 81±16 %, P<0.01 and 7±3 vs. 29±7 mmHg, P<0.05, respectively). Further, the response magnitude to mechanical stimulation tended to be greater in muscle afferents from T2D compared to control (20±7 vs. 40±8 spikes, P=0.10).CONCLUSIONSThese findings suggest that the muscle mechanoreflex is exaggerated in T2D resulting, at least in part, from augmentations in the responsiveness of thin muscle afferent fibers to mechanical stimuli. Importantly, these changes likely contribute significantly to the EPR overactivity manifest in T2D.Support or Funding InformationSupported by Lawson & Rogers Lacy Research Fund in Cardiovascular Disease and the Southwestern School of Health Professions Interdisciplinary Research Grant Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.