Hypertension and hypercholesterolemia are known risk factors for the development of atherosclerosis and are considered to influence the development of vein graft intimal hyperplasia. This study examines the effect of hypertension (two-kidney, one-clip model for 8 weeks) and hypercholesterolemia (1% cholesterol diet for 8 weeks) individually and in combination on the formation of intimal hyperplasia and the vasomotor function of vein grafts. Forty New Zealand White rabbits underwent a carotid vein bypass graft. Ten were controls, 10 were hypertensive, 10 were hypercholesterolemic, and 10 had both hypertension and hypercholesterolemia. Hypertension and/or hypercholesterolemia were present for 4 weeks prior to and for 4 weeks after surgery. All vein grafts were harvested at 4 weeks postoperatively for histology (n = 6) or contractility studies (n = 4). Compared to controls, hypercholesterolemia increased intimal but not medial thicknesses of the vein grafts and enhanced smooth muscle cell contractility. Hypertension did not increase vein graft intimal or medial thicknesses but did augment vein graft contractility compared to controls. Hypertension with hypercholesterolemia increased intimal and medial thicknesses and enhanced vasoreactivity in vein grafts. The results show that hypertension influences the vasoreactivity but not the development of intimal hyperplasia in vein grafts. When hypertension is combined with hypercholesterolemia, there is both an increase in the medial thickness and an attenuation of vasomotor function compared to hypercholesterolemia alone, although there is no further increase in intimal hyperplasia formation. Therefore, this study suggests that the combination of both atherogenic risk factors does not act synergistically in promoting either the formation of intimal hyperplasia or vasomotor dysfunction in vein grafts.
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