Interleukin-1 Type 1 Receptor Blockade Attenuates the Exaggerated Exercise Pressor Reflex in Male UC Davis Type 2 Diabetic Mellitus Rats.
JOURNAL OF PHYSIOLOGY-LONDON（2024）
Univ Texas Austin | Univ Calif Davis
Abstract
An exaggerated exercise pressor reflex and peripheral neuropathy are both evoked by the same type of thinly myelinated afferents and are present in patients with type 2 diabetes mellitus (T2DM). Although it is known that the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) contributes to peripheral neuropathy, the effects of IL-1 beta on the exercise pressor reflex in T2DM are not known. Therefore, we aimed to determine the effect of IL-1 receptors on the exercise pressor reflex in T2DM. We compared changes in peak pressor (mean arterial pressure; Delta MAP), blood pressure index (Delta BPi), heart rate (Delta HR) and heart rate index (Delta HRi) responses to static and intermittent contractions and tendon stretch before and after peripheral IL-1 type 1 receptor blockade (anakinra, Kineret (R)) in T2DM and healthy male rats and IL-1 receptor activation (IL-1 beta) in healthy rats. Blocking IL-1 receptors significantly attenuated the Delta MAP and Delta BPi to static contraction in T2DM rats. Furthermore, blocking IL-1 receptors significantly attenuated the Delta MAP, Delta BPi and Delta HRi to intermittent contraction, and Delta MAP to tendon stretch in T2DM rats (all P < 0.05). In addition, IL-1 receptor activation significantly exaggerated the Delta MAP and Delta BPi to static contraction and Delta MAP, Delta BPi and Delta HR to intermittent contraction in healthy rats, all P < 0.05. Furthermore, circulating IL-1 beta serum concentrations were significantly greater in T2DM rats than in healthy rats (P < 0.05). We conclude that IL-1 signalling contributes to the exaggerated exercise pressor reflex in T2DM, suggesting for the first time that inflammatory cytokines play a critical role in exaggerated blood pressure responses to exercise in those with T2DM.
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Key words
autonomic control of circulation,blood pressure,chronic low-grade inflammation,cytokines,mechanoreflex,metaboreflex
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