Exaggerated pressor and sympathetic responses to stimulation of the mesencephalic locomotor region and exercise pressor reflex in type 2 diabetic rats

Abstract

The cardiovascular responses to exercise are potentiated in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanisms causing this abnormality remain unknown. Central command (CC) and the exercise pressor reflex (EPR) are known to contribute significantly to cardiovascular control during exercise. Thus these neural signals are viable candidates for the generation of the abnormal circulatory regulation in this disease. We hypothesized that augmentations in CC as well as EPR function contribute to the heightened cardiovascular responses during exercise in T2DM. To test this hypothesis, changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to electrical stimulation of mesencephalic locomotor region (MLR), a putative component of the central command pathway, and activation of the EPR, evoked by electrically induced hindlimb muscle contraction, were examined in decerebrate animals. Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet (14–16 wk) in combination with two low doses (35 mg/kg week 1, 25 mg/kg week 2) of streptozotocin (T2DM). The changes in MAP and RSNA responses to MLR stimulation were significantly greater in T2DM compared with control (2,739 ± 123 vs. 1,298 ± 371 mmHg/s, 6,326 ± 1,621 vs. 1,390 ± 277%/s, respectively, P < 0.05). Similarly, pressor and sympathetic responses to activation of the EPR in diabetic animals were significantly augmented compared with control animals (436 ± 74 vs. 134 ± 44 mmHg/s, 645 ± 135 vs. 139 ± 65%/s, respectively, P < 0.05). These findings provide the first evidence that CC and the EPR may generate the exaggerated rise in sympathetic activity and blood pressure during exercise in T2DM.

Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro

“…Group IV muscle afferents are known to regulate, in part, cardiovascular and respiratory responses to exercise (Harms et al 2016), contributing significantly to expression of the skeletal muscle exercise pressor reflex . We recently demonstrated exaggerated exercise pressor reflex function in type 2 diabetes mellitus (Kim et al 2019). The findings from the present study might provide insight regarding the mechanism underlying the exaggerated reflex in type 2 diabetes mellitus in which hyperinsulinaemia is one of the pathophysiological characteristics.…”

“…We recently demonstrated exaggerated exercise pressor reflex function in type 2 diabetes mellitus (Kim et al . ). The findings from the present study might provide insight regarding the mechanism underlying the exaggerated reflex in type 2 diabetes mellitus in which hyperinsulinaemia is one of the pathophysiological characteristics.…”

Exaggerated cardiovascular responses to muscle contraction and tendon stretch in UCD type-2 diabetes mellitus rats

“…Recently, Kim et al (28) determined that the exercise pressor reflex was exaggerated in high-fat diet, low-dose streptozotocin-induced T2DM rats. Although different T2DM rat models were used, findings from Kim et al are in agreement with those from the current study.…”

Neurovascular Dysregulation During Exercise in Type 2 Diabetes

“…Although by no means direct evidence for central command involvement, these data at least suggest the possibility of heightened central command responses in T2D. A recent study (Kim et al, 2019) using a high-fat diet and streptozotocininduced T2D model in rats supports a contribution of central command in evoking exaggerated SNA and BP responses to exercise (Figure 2). These investigators reported that neural stimulation of the mesencephalic locomotor region, a putative area for the central command pathway, resulted in greater renal SNA, HR, and BP responses in T2D rats compared to controls.…”

“…In this regard, emerging evidence suggests that the exercise pressor reflex plays a prominent role in evoking exaggerated MSNA and BP responses to exercise in T2D (Figure 2). For example, T2D rats have exaggerated renal SNA and BP responses to electrically evoked static muscle contractions in the absence of central command Kim et al, 2019). Both the mechanoreflex and metaboreflex have been shown to contribute to the exaggerated exercise pressor reflex in T2D.…”