Browsing by Subject "Cardiovascular regulation"

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Effects of type 1 diabetes mellitus on the exercise pressor reflex during simulated dynamic muscle contraction : role of Piezo channels
(2020-07-28) Grotle, Ann-Katrin; Stone, Audrey J.; Tanaka, Hirofumi; Coyle, Edward F; Fadel, Paul J
The exercise pressor reflex reflexively increases sympathetic activity and blood pressure during exercise and thereby adjust the circulation to meet the metabolic demands of the working muscles. Although essential during exercise, recent studies suggest the reflex is exaggerated in early-stage type 1 diabetes mellitus (T1DM), which, in turn, increases the risk of adverse cardiovascular events. These studies have shown that T1DM leads to an exaggerated pressor reflex evoked by static muscle contraction and tendon stretch. Moreover, research suggests that Piezo channels may play a role in this exaggeration. However, it is not known whether the pressor reflex evoked by a simulated dynamic muscle is also exaggerated and whether Piezo channels play a role in eliciting this response. Therefore, the first aim of this project was to test the hypothesis that T1DM leads to an exaggerated exercise pressor reflex evoked by a simulated dynamic muscle contraction. The second aim of this project was to test the hypothesis that Piezo channels play a role in evoking the reflex pressor response to simulated dynamic muscle contraction in T1DM. We used a streptozotocin (50 mg/kg) induced T1DM model and unanaesthetized, decerebrate rats, to measure cardiovascular reflex changes in healthy and T1DM rats. We compared these changes between groups for aim 1 and before and after locally injecting GsMTx-4 (0.25 μM), a Piezo channel blocker, into the vasculature of the hindlimb for aim 2. The major findings from this study are: 1) early-stage T1DM leads to an exaggerated reflex pressor response to simulated dynamic muscle contraction, and 2) Piezo channel blockade attenuates the reflex pressor response by 33%. Notably, the Piezo channel blockade attenuated both the early onset exaggeration and the blood pressure index in T1DM rats, which suggest it effectively reduce cardiovascular strain during a simulated dynamic muscle contraction in T1DM. These findings are significant as they provide novel insight into the effects of T1DM on the reflexive control of the circulation and provide a potential mechanism mediating these adverse effects. Thus, the information gained from this project offers a mechanistic target for the development of effective therapeutic strategies aimed at reducing the heightened cardiovascular risk in this population