Dietary probucol preserves endothelium-dependent relaxation of arteriovenous fistula in hypercholesterolemic rabbits.

BACKGROUND Shear stress caused by arteriovenous fistula (AVF) enhances endothelium-dependent relaxation (EDR) but oxidized low-density lipoprotein (ox- LDL) counteracts its effect. Probucol, a lipid soluble antioxidant, may preserve EDR of AVF by limiting oxidation of LDL. METHODS Twenty New Zealand rabbits, fed with 2% cholesterol chow for 4 weeks, underwent AVF. They were then divided into two groups: continuing with 2% cholesterol chow alone (group I) and 2% cholesterol chow with 1% probucol supplement (group II). Another 10, fed regular chow, were assigned to the control (group III). The levels of cholesterol and LDL were measured. Segments of the AVF afferent arteries were harvested to check intimal thickness, and endothelium-dependent and independent relaxations, after 4 weeks dietary treatment had been completed. RESULTS Both cholesterol and LDL levels were significantly elevated after 4 weeks of cholesterol feeding. These profiles reached higher levels at 8 weeks in group I and were less increased in group II. The intimal hyperplasia ratio was 48% in group I, 34% in group II and 24% in group III. Maximal EDR response to either acetylcholine or receptor-independent calcium ionophore A23187 in group II was greater than that in group I (66 +/- 1.9% versus 38 +/- 1.2%, p = 0.02; 76 +/- 2.4% versus 30 +/- 0.8%, p = 0.01) and not different from that in group III (74 +/- 2.4%, 84 +/- 3.7%). There was no similar difference of denuded arterial rings among the three groups (76 +/- 3.2%, 78 +/- 3.7%, 82 +/- 4.1%). CONCLUSION Cholesterol can limit EDR of AVF and produce vulnerability to early occlusion and thrombosis. Probucol supplement under hyperlipidemia status preserves EDR and not endothelium-independent relaxation.