Exaggerated Exercise Pressor Reflex During the Progression of Type 2 Diabetes Mellitus is Independent of Aging

Abstract

We previously determined that the exercise pressor reflex and mechanoreflex are exaggerated during the progression of type 2 diabetes mellitus (T2DM) in UCD‐T2DM rats. For this first study T2DM onset was determined using a non‐fasting glucose threshold of 200 mg/dL. Importantly, aging, which may also be associated with autonomic modulation changes, was not investigated during this previous study. Therefore, the objective of the current study was to determine if these changes in the exercise pressor reflex during T2DM progression occur independent of aging. We hypothesized that the exercise pressor reflex and mechanoreflex would remain exaggerated during the progression of T2DM when compared against age‐matched healthy controls. Methods Studies were conducted in fasted, unanesthetized, decerebrated UCD‐T2DM rats, using a fasting glucose of 140 mg/dL as diagnostic criteria, at 4 different time points of disease progression (pre‐onset: before developing diabetes; early‐onset: 3‐7 wks after onset; established: 23‐28 wks after onset; and chronic: 39‐44 wks after onset). Healthy, age‐matched Sprague Dawley rats were used as controls (CTL). The exercise pressor reflex was evoked by statically and intermittently contracting the hindlimb for 30 s, and the mechanoreflex was evoked by stretching the Achilles tendon for 30 s. Peak changes in mean arterial pressure (MAP) and developed tension were measured and compared across all groups (one‐way ANOVA followed by Holm Sidak's post hoc analysis). Results We found that fasting blood glucose was significantly higher after the onset of T2DM and remained above the diagnostic threshold (140 mg/dL) during the progression of the disease (p<0.05). Static hindlimb muscle contraction significantly increased peak pressor response in early‐onset UCD‐T2DM rats, but not in other stages of T2DM, compared to age‐matched healthy controls (CTL: 10 ± 1 mmHg, n=7; T2DM: 24 ± 5 mmHg, n=6, p<0.05) with similar developed tensions, p>0.05. Likewise, intermittent hindlimb muscle contraction significantly increased peak pressor response in early‐onset UCD‐T2DM rats, but not later stages of T2DM, compared to their age‐matched healthy controls (CTL: 9 ± 1 mmHg, n=6; T2DM: 36 ± 7 mmHg, n=4, p<0.05) with similar developed tensions, p>0.05. Similarly, passive tendon stretch significantly increased peak pressor response in early‐onset UCD‐T2DM rats, but not later stages of T2DM, compared to their age‐matched healthy controls (CTL: 12 ± 5 mmHg, n=6; T2DM: 36 ± 8 mmHg, n=7, p<0.05) with similar developed tensions, p>0.05. Conclusion These findings suggest that the exercise pressor reflex and mechanoreflex are exaggerated at the onset of T2DM, as diagnosed by fasted glucose of 140mg/dL, but not later in the disease, and this change occurs independent of aging.