Parallel exercise training reverses vascular dysfunction in hypercholesterolemic rabbits

Yang AL1, Jen CJ1,2, and Chen HI1,2*

Institute of Basic Medical Sciences1, Department of Physiology2, National Cheng

Kung University, Tainan 701, TAIWAN

Motivation

Endothelial dysfunction is an early event in atherosclerosis.Expression of pro-inflammatory molecules is upregulated in atherosclerosis.Chronic exercise enhances endothelium-dependent vasodilating responses in normal or hypertensive animals.

We hypothesize that chronic exercise improves vascular endothelial function and reduces the expression of pro-inflammatory molecules in hypercholesterolemic rabbits at early stages.

Methods I

• Animal models: Male New Zealand White rabbits were divided into 4

groups: normal diet control(N); 2% high cholesterol diet control(H); normal diet with exercise(NE); and high cholesterol diet with exercise(HE).

• Exercise protocol: Rabbits in exercise groups received running exercise

training on a leveled treadmill for 2, 4, 6, or 8 weeks in total.

Methods II

• Oil red O staining: to determine lipid deposition as fatty streaks

• Dose responses of ACh–induced vasorelaxation in aortas

• Immunostaining of pro-inflammatory molecules, i.e., adhesion molecules (P-selectin, VCAM-1), MCP-1, and iNOS

Oil red O-stained thoracic aortas (8 wk intervention)

N H

NE HE

---------------------------------------------------------------------------------- Lipid Deposit (% surface area)Group ------------------------------------------------------------------------ 2wk 4wk 6wk 8wk----------------------------------------------------------------------------------H 1.5+0.3(6) 26+10(5) 32+8(9) 48+10(9)HE 1.5+1.0(6) 8+3 (6)* 11+5(9)* 40+8(9)----------------------------------------------------------------------------------Data are expressed as mean +SEM.Numbers in the parentheses indicate the numbers of animals used in each group.* P<0.05 (HE vs. H)

Exercise reduces high-cholesterol diet-evoked lipid deposition in rabbit aortas

High cholesterol diet feeding impairs vasorelaxation,whereas concomitant exercise reduces the impairment

Immunostaining of pro-inflammatory molecules (6 wk intervention)

100m

----------------------------------------------------------------------------------Group P-selectin VCAM-1 MCP-1 iNOS----------------------------------------------------------------------------------4wkH 1.67+0.40 1.85+0.45 1.27+0.45 1.22+0.37HE 0.38+0.15* 0.23+0.15* 0.36+0.18* 0.28+0.14*6wkH 2.22+0.35 1.63+0.21 1.76+0.28 2.42+0.23HE 0.87+0.35* 0.43+0.14* 0.55+0.18* 0.93+0.36*8wkH 1.95+0.44 1.68+0.23 2.27+0.30 2.33+0.27HE 0.73+0.19* 1.07+0.14* 1.28+0.21* 1.25+0.10**----------------------------------------------------------------------------------Data are expressed as mean +SEM. * P<0.05; **P<0.01 (HE vs. H)

Exercise reduces high-cholesterol diet-induced protein expression in rabbit aortas

Conclusion

High cholesterol diet feeding induces lipid deposition and the expression of pro-inflammatory molecules, and impairs vascular responsiveness.

Parallel exercise training ameliorates vascular structural changes and improves endothelial function in hypercholesterolemia.

Bibliography

Yang AL, Chen HI. Chronic exercise reduces adhesion molecules/iNOS expression and partially reverses vascular responsiveness in hypercholesterolemic rabbit aortae. Atherosclerosis 2003

Yang AL, Jen CJ, Chen HI. Effects of high cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study. J Appl Physiol 2003