Exaggerated Cardiovascular Response to Muscle Mechanoreflex Activation in Type 2 Diabetic Rats

Abstract

Evidence suggests that the cardiovascular response to physical activity is excessively heightened in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms underlying this exaggerated circulatory responsiveness remain to be fully elucidated. The exercise pressor reflex (EPR) is a primary contributor to autonomic cardiovascular regulation during physical exercise. Mechanically (mechanoreflex) and metabolically (metaboreflex) sensitive components mediate EPR function. We have shown previously that the metaboreflex is overactive in T2DM whereas the function of the mechanoreflex remains undetermined in this disease. PURPOSE: To assess mechanoreflex activity in T2DM rats. It was hypothesized that the heightened cardiovascular response to exercise in T2DM is induced, in part, by functional alterations in the muscle mechanoreflex. METHODS: T2DM was induced in Sprague-Dawley rats by a combination of both a low-dose streptozotocin injection (30-35 mg/kg, ip) and a 14-16 wk high-fat diet. In control rats (normal diet; no steptozotocin; n=34) and T2DM (n=10) rats, the EPR was activated by electrically-inducing hindlimb muscle contraction via stimulation of spinal ventral roots. The mechanically-sensitive component of the EPR was selectively activated by passively stretching hindlimb muscle. RESULTS: Compared to control animals, sympathetic and pressor responses to EPR activation were significantly greater in T2DM rats (RSNA: Δ=122±20 vs. 61±8 %, P<0.05; MAP: Δ=49±5 vs. 20±2 mmHg, P<0.05). Passive stretch likewise evoked greater increases in RSNA (Δ=81±16 vs. 31±5 %, P<0.05) and MAP (Δ=38±7 vs. 13±2 mmHg, P<0.05) in T2DM rats compared to healthy controls. CONCLUSIONS: These data demonstrate the skeletal muscle mechanoreflex is overactive in T2DM. This is an important finding as it suggests that both the metaboreflex (as previously reported) and mechanoreflex contribute significantly to the generation of EPR overactivity in T2DM possibly accounting for the abnormally large cardiovascular response to exercise in this disease. Supported by the Lawson & Rogers Lacy Research Fund in Cardiovascular Disease