Moderate-Intensity Exercise Improves Mesenteric Arterial Function in Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats: A Shift in the Relative Importance of Endothelium-Derived Relaxing Factors (EDRF)

Figures

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  Figure 1. Effects of MIE on metabolic parameters of sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. (A) Body weight; (B) adipose tissue to body weight ratio; (C) triglyceride level; (D) blood glucose level; (E) HbA1c (%); (F) insulin level. Values are represented as mean ± SEM. Each bar represents the values obtained from n = 5–7 animals per group. Capped lines indicate significant differences between two groups (* p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001), analyzed by one-way ANOVA followed by Tukey’s post hoc test.

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  Figure 2. Relaxation responses to cumulative concentrations of acetylcholine (ACh, 10−8 to 10−5 M) in intact mesenteric arterial rings precontracted with phenylephrine (PE, 2 µM) from sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Data are expressed as mean ± SEM; n = 5–8 animals per group. Brackets indicate significant differences between groups (p < 0.05), analyzed using two-way ANOVA with repeated measures followed by Tukey’s post hoc test.

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  Figure 3. Effects of inhibiting cyclooxygenase (COX), nitric oxide synthase (NOS), small-conductance and intermediate-conductance calcium-activated potassium channels (SKCa and IKCa) on acetylcholine (ACh)-induced vasorelaxation in mesenteric arteries taken from sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats; (A) CS, (B) CE, (C) DS, and (D) DE group. CRC to ACh (10−8 to 10−5 M) was generated in the absence of an inhibitor (no drug) or in the presence of Indo, Indo + L-NAME (I + L), and Indo + L-NAME + Apamin + TRAM-34 (I + L + A + T) in mesenteric arterial rings. Indo (indomethacin; 10 µM), L-NAME (Nω-nitro-L-arginine methyl ester; 200 µM), Apamin (1 µM), TRAM-34 [1-[(2-Chlorophenyl) diphenylmethyl]-1H-pyrazole; 1 µM]. * (p < 0.05) vs. no drug; # (p < 0.05) vs. Indo; $ (p < 0.05) vs. Indo + L-NAME, analyzed using two-way ANOVA with repeated measures followed by Bonferroni post hoc test.

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  Figure 4. Western blot analysis of (A) COX-1 and (B) COX-2 expression in mesenteric arteries of sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Protein levels were quantified by densitometry and normalized to the corresponding GAPDH. Values are represented as mean ± SEM. Each bar represents the values obtained from n = 3–4 animals per group. Representative bands of target and housekeeping proteins (GAPDH) were shown from the same membrane. Capped lines indicate significant differences between two groups (* p < 0.05, and ** p < 0.01), analyzed using one-way ANOVA followed by Tukey’s post hoc test. COX-1, cyclooxygenase-1; COX-2, cyclooxygenase-2.

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  Figure 5. Western blot analysis of eNOS expression in mesenteric arteries of sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Protein levels were quantified by densitometry and normalized to the corresponding GAPDH. Values are represented as mean ± SEM. Each bar represents the values obtained from n = 4–5 animals per group. Representative bands of target and housekeeping proteins (GAPDH) were shown from the same membrane. Capped lines indicate significant differences between two groups (** p < 0.01, *** p < 0.001, and **** p < 0.0001), analyzed using one-way ANOVA followed by Tukey’s post hoc test. eNOS, endothelial nitric oxide synthase.

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  Figure 6. Western blot analysis of (A) IKCa (KCa3.1) and (B) SKCa (KCa2.3) expressions in mesenteric arteries of sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Protein levels were quantified by densitometry and normalized to the corresponding GAPDH. Values are represented as mean ± SEM. Each bar represents the values obtained from n = 4–5 animals per group. Representative bands of target and housekeeping proteins (GAPDH) were shown from the same membrane. Capped lines indicate significant differences between two groups (* p < 0.05), analyzed by one-way ANOVA followed by Tukey’s post hoc test. The top right section of B shows a comparison of only diabetic groups (DS vs. DE) which was analyzed by Student’s unpaired t-test. IKCa, intermediate conductance calcium activated potassium channel; SKCa, small conductance calcium activated potassium channel.

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  Figure 7. Contractile responses to cumulative concentrations of phenylephrine (PE, 10−8 to 10−5 M) in intact mesenteric arterial rings from sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Data are expressed as mean ± SEM; n = 5–6 animals per group. # p < 0.05 (vs. CS), * p < 0.05 (vs. CE), and $ p < 0.05 (vs. DE), analyzed using two-way ANOVA with repeated measures followed by Tukey’s post hoc test.

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  Figure 8. Myogenic tone (%) at different intraluminal pressures in intact mesenteric arterial rings from sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Data are expressed as mean ± SEM; n = 5–8 animals per group. # p < 0.05 (vs. CS), * p < 0.05 (vs. CE), and $ p < 0.05 (vs. DE), analyzed using two-way ANOVA with repeated measures followed by Tukey’s post hoc test.

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  Figure 9. Wall thickness at different intraluminal pressures in intact mesenteric arterial rings from sedentary and exercise-trained control (CS and CE) and diabetic (DS and DE) rats. Data are expressed as mean ± SEM; n = 5–8 animals per group. # p < 0.05 (vs. CS), * p < 0.05 (vs. CE), and $ p < 0.05 (vs. DE), analyzed using two-way ANOVA with repeated measures followed by Tukey’s post hoc test.