(890.3) Pro-inflammatory Cytokine IL-1β Contributes to the Exaggerated Exercise Pressor Reflex in UC, Davis-Type 2 Diabetes Mellitus Rats

Poster Board Number: E370

Yu Huo (the University of Texas at Austin), Balyssa Bell (the University of Texas at Austin), Milena Samora (the University of Texas at Austin), James Graham (University of California, Davis), Kimber Stanhope (University of California, Davis), Peter Havel (University of California, Davis), Michelle Harrison (the University of Texas at Austin), Audrey Stone (the University of Texas at Austin)

Studies have shown that pressor responses to muscle contraction and tendon stretch are exaggerated in type 2 diabetes mellitus (T2DM). Low-grade inflammation, which contributes to the underlying pathology of T2DM, involves an increase in pro-inflammatory cytokines. These cytokines are known to play a role in exaggerating the pressor response during muscle contraction and tendon stretch. Although a previous study found that the pro-inflammatory cytokine, interleukin-1 beta (IL-1β) is increased in the serum of individuals with T2DM, it is not known whether changes in IL-1β in the presence of low-grade inflammation play a role in exaggerating the exercise pressor reflex in T2DM. Therefore, the purpose of this study was to determine the effects of IL-1β on the pressor responses evoked by skeletal muscle contraction and tendon stretch in T2DM rats. We hypothesized that IL-1β plays a role in exaggerating the pressor response to muscle contraction and tendon stretch in T2DM rats. Methods. The exercise pressor reflex was evoked by statically and intermittently contracting the hindlimb for 30 s, and the mechanoreflex was evoked by passively stretching the Achilles tendon for 30 s. We first evoked the exercise pressor reflex and mechanoreflex before and after activating IL-1 receptors by injecting IL-1β (5ng/uL) into the hindlimb circulation of working skeletal muscles in healthy unanesthetized, decerebrated male Sprague Dawley rats. We then evoked the exercise pressor reflex and mechanoreflex before and after blocking IL-1 receptors using Kineret (1ug/100ul), an IL-1 receptor antagonist, in fasted, unanesthetized, decerebrated male UCD-T2DM rats. Peak changes in mean arterial pressure and heart rate were measured and compared before and after injecting IL-1β or Kineret. Results. In healthy rats, activating IL-1 receptors by injecting IL-1β significantly increased the peak pressor response to static contraction (before: 12 ± 1, after: 24 ± 2 mmHg, n=8, plt;0.05) and intermittent contraction (before: 9 ± 1, after: 17 ± 2 mmHg, n=8, plt;0.05), but not stretch (before: 12 ± 2, after: 13 ± 2 , n=9, p=0.23), although the cardioaccelerator response to intermittent contraction was significantly lower after IL-1β injection (before: 18 ± 3, after: 14 ± 2 bpm, n=8, plt;0.05). Furthermore, in UCD-T2DM rats, blocking IL-1 receptors significantly attenuated the pressor and cardioaccelerator responses to static contraction (pressor: before: 29 ± 4, after: 13 ± 3 mmHg; cardioaccelerator: before: 36 ± 8, after: 14 ± 2 bpm; n=5, plt;0.05), intermittent contraction (pressor: before: 23 ± 5, after: 9 ± 2 mmHg; cardioaccelerator: before: 43 ± 11, after: 21 ± 6 bpm n=4, plt;0.05), and stretch (pressor: before: 22 ± 9, after: 13 ± 6 mmHg; cardioaccelerator: before: 34 ± 8, after: 14 ± 4 bpm n=4, plt;0.05). The developed tension was similar for all comparisons. Conclusion. These findings suggest that IL-1β plays a role in exaggerating the pressor response to muscle contraction and tendon stretch in T2DM rats.

This project was supported by NIH R01 HL144723.