Effects of type 1 diabetes on reflexive cardiovascular responses to intermittent muscle contraction

Abstract

Studies have shown that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated reflex pressor response to both static muscle contraction and tendon stretch. However, whether similar responses are present during dynamic exercise (i.e., intermittent contraction) is not known. Therefore, the purpose of this study was to determine whether T1DM leads to an exaggerated reflex pressor response to intermittent muscle contraction. We measured the exercise pressor reflex in unanesthetized, decerebrated T1DM (Streptozotocin 50 mg/kg; STZ) and healthy control (CTL) Sprague Dawley rats by intermittently contracting the hindlimb muscles for 30 s while measuring mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). Intermittently contracting the hindlimb muscles evoked exaggerated mean RSNA (STZ: Δ109 ± 21%, n=4; CTL: Δ61 ± 8%, n=5, p<0.05), peak MAP (STZ: Δ32 ± 2 mmHg, n=9; CTL: Δ12 ± 2 mmHg, n=6, p<0.05), blood pressure index (STZ: Δ625 ± 60 mmHg·s, n=9; CTL: Δ241 ± 46 mmHg·s, n=6, p<0.05), and HR (STZ: Δ24 ± 3 bpm, n=9; CTL: Δ9 ± 3 bpm, n=6, p<0.05) responses to similar developed tensions (p>0.05) in T1DM compared to CTL rats. T1DM rats also exhibited exaggerated early-onset sympathetic (onset: 1 s) and pressor (onset: 5 s) responses. These data show that early-stage T1DM leads to an exaggerated pressor reflex evoked by intermittent muscle contraction. The early onset and greater blood pressure index suggest that cardiovascular strain during dynamic exercise may be significantly higher in individuals with T1DM.

Altered Cardiovascular Responses to Exercise in Type 1 Diabetes

“…T1D presents an exaggerated BP response to exercise (2,24) and it is mediated, in part, by an overactive exercise pressor reflex (9–12). Although there is convincing evidence implicating alterations in the muscle metaboreflex (1), mechanoreflex (9), skeletal muscle afferent sensitivity (12), and mechano-gated Piezo channels (9,11), further studies are needed to better understand the precise mechanisms leading to these alterations.…”

“…This is important because dynamic exercise is widely included in the exercise prescription as a treatment in the management of T1D (8). Grotle et al (2020) (10) recently tested the effect of T1D on the exercise pressor reflex evoked by simulated dynamic muscle contractions (i.e., intermittent muscle Figure 1. A schematic figure of the exercise pressor reflex mediating the altered cardiovascular responses to exercise in type 1 diabetes (T1D).…”

“…The exaggerated BP response to exercise in T1D is mediated, at least in part, by an overactive exercise pressor reflex (9,10,12,24). Although this neural mechanism might not be affected by acute changes in glucose level (43), hyperglycemia has been shown to alter the responsiveness of thin skeletal muscle afferent fibers in type 2 diabetes rats via protein kinase C (PKC) signaling pathway, which might contribute to the abnormally enhanced BP response to exercise in diabetes (44).…”

“…Overall cardiometabolic benefits of exercise make it a highly recommended treatment strategy in the clinical management of T1D (8). However, previous studies in animals (9)(10)(11)(12) and one study in T1D patients (2) indicate that diabetics may be at a heightened risk of experiencing exaggerated cardiovascular responses to exercise, which in turn, increases the risk of acute cardiovascular events. For example, a population-based followup study suggested that a systolic blood pressure (BP) exceeding 230 mm Hg during exercise is associated with a 2.47-fold greater risk of acute myocardial infarction (13), and an increase of greater than 19.7 mm Hg•min −1 of exercise has a 2.3-fold increased risk of stroke (14).…”

“…Emerging evidence suggests that T1D has an altered cardiovascular response to muscle contraction, in part, due to an exaggerated exercise pressor reflex (9,10,12,24). In addition, there is one study describing an attenuated cardiovascular response to the isolated metabolic component of the exercise pressor reflex in T1D patients (1).…”