Atherosclerosis, 89 ( 199 1) 223-230 0 1991 Elsevier Scientific Publishers Ireland, Ltd. 0021-9150/91/$03.50 ADONIS 002191509100153Y 223 ATHERO 04683 Aortic response to relaxing agents in Watanabe heritable hyperlipidemic (WHHL) rabbits of different age A. Chinellato ‘, N. Banchieri ‘, L. Pandolfo I, E. Ragazzi ‘, G. Froldi ‘, F. Norido ‘, L. Caparrotta ’ and G. Fassina ’ ’Department of Pharmacology, lJnit,ersity of Padol,a, I-35131 Padoc,a (Italy). and 2 FIDlA Research Laboratories, Ahano Terme (Italy) (Received 21 January, 1991) (Revised, received 14 May, 1991) (Accepted 16 May. 1991) Summary 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 choles- terol was elevated (626 + 99 mg/lOO ml) in 4-6-month-old WHHL rabbits and significantly lower in 12-14-month-old animals (344 + 51 mg/lOO ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 f 0.3 mg/lOO mg fresh tissue vs. 0.08 i 0.003 mg/lOO 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 PM) on EC,,, 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-l I- ( - 357~ 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 FM 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 NaNO, (10 PM 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 compen- satory responses evolve during atherogenesis to maintain the vasodilator function. Key words: Aortic relaxation; Age; Acetylcholine; ATP; Sodium nitrite; Atherosclerosis; WHHL rabbits Correspondence to; L. Caparrotta, Department of Pharma- cology. University of Padua, Largo E. Meneghetti 2, I-35131 Padova, Italy. Fax: (049) 831878.