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

Abstract

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.

Keywords: autonomic control of circulation; blood pressure; cardiovascular response; mechanoreflex; metaboreflex.

FIGURE 1

Means ± SE and individual data points showing that statically contracting the hindlimb muscles evoked exaggerated peak pressor (A) and cardioaccelerator responses (B) during the early onset stage in male T2DM rats compared to healthy, age-matched controls. Two-way ANOVA with Holm-Sidak’s post hoc comparisons (*) p < 0.05 indicates significant increase relative to age-matched control.

FIGURE 2

The change in MAP (A) and HR (C) baseline were averaged second by second to show the temporal changes during 30 s of static contraction in male T2DM rats and healthy, age-matched controls. ΔBPi (B) and ΔHRi (D) were then calculated over the 30 s of contraction to determine the difference between T2DM rats and healthy, age-matched controls at all stages. The ΔBPi and ΔHRi were greater in the T2DM rats compared to healthy, age-matched controls during the early onset stage of T2DM. Two-way ANOVA with Holm-Sidak’s post hoc comparisons (*) p < 0.05 indicates significant increase relative to age-matched control.

FIGURE 3

Means ± SE and individual data points showing that intermittently contracting the hindlimb muscles evoked a similar peak pressor (A) and cardioaccelerator responses (B) in male T2DM rats compared to their healthy, age-matched controls during all stages of T2DM. Two-way ANOVA with Holm-Sidak’s post hoc comparisons.

FIGURE 4

The change in MAP (A) and HR (C) from baseline were averaged second by second to show the temporal changes during 30 s of intermittent contraction in male T2DM rats and healthy, age-matched controls. ΔBPi (B) and ΔHRi (D) were then calculated over the 30 s of contraction to determine the difference between T2DM rats and healthy, age-matched controls at all stages. The ΔBPi and ΔHRi were greater in the T2DM rats compared to healthy, age-matched controls during the early onset stage of T2DM. The ΔHRi was significantly lower in the T2DM rats compared to healthy, age-matched controls during the established and chronic stage. Two-way ANOVA with Holm-Sidak’s post hoc comparisons (*) p < 0.05 indicates significant increase relative to age-matched control (#) p < 0.05 indicates significant decrease relative to age-matched control.

FIGURE 5

Means ± SE and individual data points showing that stretching the hindlimb muscles evoked an exaggerated peak pressor (A) during the early onset stage in male T2DM rats compared to healthy, age-matched controls. Cardioaccelerator responses (B) were similar within groups. Two-way ANOVA with Holm-Sidak’s post hoc comparisons (*) p < 0.05 indicates significant increase relative to age-matched control.

FIGURE 6

The change in MAP (A) and HR (C) from baseline were averaged second by second to show the temporal changes during 30 s of tendon stretch in male T2DM rats and healthy, age-matched controls. ΔBPi (B) and ΔHRi (D) were then calculated over the 30 s of contraction to determine the difference between T2DM rats and healthy, age-matched controls at all stages. The ΔBPi and ΔHRi were greater in the T2DM rats compared to healthy, age-matched controls during the early onset stage of T2DM. Two-way ANOVA with Holm-Sidak’s post hoc comparisons (*) p < 0.05 indicates significant increase relative to age-matched control.