Statin treatment prevents beneficial adaptations obtained following accustomed exercise.

<p>(A) PGC-1α mRNA and (B) mitochondrial DNA content in gastrocnemius muscles, and (C) plasma 4-HNE after normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). Means ± SD; n = 8-10/group. † = main effect of statin p<0.05; ^<b>§</b> = statin x exercise interaction, p<0.05; ^a,b,c = different letters indicate statistically significant differences at 95% confidence.</p

Effect of statin treatment and exercise on cholesterol, voluntary running wheel activity, and maximal grip strength.

<p>ApoE^-/- mice were evaluated following normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). (A) Cholesterol level at the end of the intervention, (B) running wheel distance for novel exercise group, (C) running wheel distance for accustomed group, (D) grip strength, and (E) change in grip strength from beginning to end of study. E: ApoE^-/-, Z: Zocor (simvastatin), S: Saline, S: Sedentary, N: Novel, A: Accustomed. Means ± SD; n = 8-10/group. † = main effect of statin, p<0.05; ^# = statin x time interaction, p<0.05; * = within group pairwise comparison, p<0.05.</p

Body Weight.

<p>Body Weight.</p

Statin treatment does not significantly impact fiber type specific cross sectional area.

<p>(A) Average myofiber CSA (all types combined), (B) representative image of CSA staining, (C) average Type 2A CSA, (D) average Type 2B CSA, and (E) average Type 2X CSA after normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). Representative images of fiber types in muscle are presented for (E). Means ± SD; n = 4-6/group. ^<b>§</b> = statin x exercise interaction, p<0.05; ^a,b = different letters indicate statistically significant differences at 95% confidence.</p

Treatment groups based on combinations of cholesterol level, exercise, and statin treatment over days 1–14 and days 15–28.

<p>Treatment groups based on combinations of cholesterol level, exercise, and statin treatment over days 1–14 and days 15–28.</p

Exercise hemodynamic and water intake.

<p>Exercise hemodynamic and water intake.</p

A schematic of the study design showing the procedures for each visit.

<p>Subjects underwent testing to determine peak oxygen uptake (VO_2peak) and a blood draw prior to randomization to placebo or histamine blockade (Visit 1). The order in which the blockade/placebo (visits 2 or 3) were administered was randomized. During study visits 2 and 3, cardiovascular (CV) measurements were obtained at rest and at 30 min, 60 min and 90 min post-exercise (during recovery).</p

Systemic vascular conductance (SVC) at baseline and at 30 min, 60 min and 90 min following aerobic exercise in the control condition (A) and H₁R and H₂R blockade condition (B).

<p>* Significant blockade by time interaction. § Significant main effect of time (p<0.05). ‡ BL had significantly lower SVC compared to CA at PRE in the blockade condition (p<0.05).</p

Subject characteristics.

<p>Subject characteristics.</p