Aortic response to relaxing agents in Watanabe heritable hyperlipidemic (WHHL) rabbits of different age

Serum and aortic tissue cholesterol levels in parallel with aortic relaxation to endothelium-dependent and independent drugs were determined in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand (N.Z.) normocholesterolemic rabbits, aged 4–14 months. Serum cholesterol was elevated (626 ± 99 mg/100 ml) in 4–6-month-old WHHL rabbits and significantly lower in 12–14-month-old animals (344 ± 51 mg/100 ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 ± 0.3 mg/100 mg fresh tissue vs. 0.08 ± 0.003 mg/100 mg, respectively) and it did not vary with age. In N.Z. rabbits, serum and aortic cholesterol levels were low from 4 to 14 months of age. The aortic relaxation to acetylcholine (0.03–3 μM) on EC 50 noradrenaline precontracted rings was similar in 4–6-month-old WHHL and N.Z. rabbits of the same age. In WHHL rabbits, the relaxation to acetylcholine was significantly reduced in 7–11- (-35% at maximum) and in 12–14-month-old rabbits (−40% at maximum). In N.Z. rabbits the response to acetylcholine was not modified in the 3 age groups. The relaxation to ATP (30 μM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits, but in 12–14-month-old WHHL rabbits the maximal relaxating response was significantly more elevated than in age-matched N.Z. rabbits (50.1 ± 2.5% vs. 35.1 ± 3.2%, respectively). The aortic relaxation to NaN0 2 (10 μM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits. The aortic rings of young WHHL were more responsive to all vasodilator drugs, in comparison with age-matched normocholesterolemic rabbits. The results suggest that, with the loss of endothelium-dependent dilator function in hereditable hyperlipidemic rabbits, other compensatory responses evolve during atherogenesis to maintain the vasodilator function.