Spontaneous baroreflex sensitivity is attenuated in male UCD-type 2 diabetes mellitus rats: A link between metabolic and autonomic dysfunction.

Patients with type 2 diabetes mellitus (T2DM) have impaired arterial baroreflex function, which may be linked to the co-existence of obesity. However, the role of obesity and its related metabolic impairments on baroreflex dysfunction in T2DM is unknown. This study aimed to investigate the role of visceral fat and adiponectin, the most abundant cytokine produced by adipocytes, on baroreflex dysfunction in T2DM rats. Experiments were performed in adult male UCD-T2DM rats assigned to the following experimental groups (n = 6 in each): prediabetic (Pre), diabetes-onset (T0), 4 weeks after onset (T4), and 12 weeks after onset (T12). Age-matched healthy Sprague-Dawley rats were used as controls. Rats were anesthetized and blood pressure was directly measured on a beat-to-beat basis to assess spontaneous baroreflex sensitivity (BRS) using the sequence technique. Dual-energy X-ray absorptiometry (DEXA) was used to assess body composition. Data are presented as mean ± SD. BRS was significantly lower in T2DM rats compared with controls at T0 (T2D: 3.7 ± 3.2 ms/mmHg vs Healthy: 16.1 ± 8.4 ms/mmHg; P = 0.01), but not at T12 (T2D: 13.4 ± 8.1 ms/mmHg vs Healthy: 9.2 ± 6.0 ms/mmHg; P = 0.16). T2DM rats had higher visceral fat mass, adiponectin, and insulin concentrations compared with control rats (all P < 0.01). Changes in adiponectin and insulin concentrations over the measured time-points mirrored one another and were opposite those of the BRS in T2DM rats. These findings demonstrate that obesity-related metabolic impairments may contribute to an attenuated spontaneous BRS in T2DM, suggesting a link between metabolic and autonomic dysfunction.

Exaggerated exercise pressor reflex in male UC Davis type 2 diabetic rats is due to the pathophysiology of the disease and not aging.

Introduction: Studies in humans and animals have found that type 2 diabetes mellitus (T2DM) exaggerates the blood pressure (BP) response to exercise, which increases the risk of adverse cardiovascular events such as heart attack and stroke. T2DM is a chronic disease that, without appropriate management, progresses in severity as individuals grow older. Thus, it is possible that aging may also exaggerate the BP response to exercise. Therefore, the purpose of the current study was to determine the effect of the pathophysiology of T2DM on the exercise pressor reflex independent of aging. Methods: We compared changes in peak pressor (mean arterial pressure; ΔMAP), BP index (ΔBPi), heart rate (ΔHR), and HR index (ΔHRi) responses to static contraction, intermittent contraction, and tendon stretch in UCD-T2DM rats to those of healthy, age-matched Sprague Dawley rats at three different stages of the disease. Results: We found that the ΔMAP, ΔBPi, ΔHR, and ΔHRi responses to static contraction were significantly higher in T2DM rats (ΔMAP: 29 ± 4 mmHg; ΔBPi: 588 ± 51 mmHg•s; ΔHR: 22 ± 5 bpm; ΔHRi: 478 ± 45 bpm•s) compared to controls (ΔMAP: 10 ± 1 mmHg, p < 0.0001; ΔBPi: 121 ± 19 mmHg•s, p < 0.0001; ΔHR: 5 ± 2 bpm, p = 0.01; ΔHRi: 92 ± 19 bpm•s, p < 0.0001) shortly after diabetes onset. Likewise, the ΔMAP, ΔBPi, and ΔHRi to tendon stretch were significantly higher in T2DM rats (ΔMAP: 33 ± 7 mmHg; ΔBPi: 697 ± 70 mmHg•s; ΔHRi: 496 ± 51 bpm•s) compared to controls (ΔMAP: 12 ± 5 mmHg, p = 0.002; ΔBPi: 186 ± 30 mmHg•s, p < 0.0001; ΔHRi: 144 ± 33 bpm•s, p < 0.0001) shortly after diabetes onset. The ΔBPi and ΔHRi, but not ΔMAP, to intermittent contraction was significantly higher in T2DM rats (ΔBPi: 543 ± 42 mmHg•s; ΔHRi: 453 ± 53 bpm•s) compared to controls (ΔBPi: 140 ± 16 mmHg•s, p < 0.0001; ΔHRi: 108 ± 22 bpm•s, p = 0.0002) shortly after diabetes onset. Discussion: Our findings suggest that the exaggerated exercise pressor reflex and mechanoreflex seen in T2DM are due to the pathophysiology of the disease and not aging.