DIFFERENCES IN ENDOTHELIUM-DEPENDENT RELAXATION IN VARIOUS ARTERIES FROM WATANABE HERITABLE HYPERLIPIDEMIC RABBITS WITH INCREASING AGE

1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A23187 was examined in aorta, coronary, bas ilar and renal arteries isolated from Watanabe heritable hyperlipidaem ic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic h eterozygous WHHL rabbits as controls. 2. In the rings of WHHL rabbit a ortae and coronary arteries preconstricted with vasoconstrictors, endo thelium-dependent relaxation in response to ACh was attenuated with ag e compared to the heterozygous WHHL rabbits. A significant negative co rrelation was found between the total cholesterol content and the rela xation response to ACh in the aortae or coronary arteries from 6 and 1 2 month old WHHL rabbits. 3. In the rings of basilar arteries, endothe lium-dependent relaxations to ACh were not modified with age. Similarl y in the rings of renal arteries, the relaxation response to ACh was n ot changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at h igher concentrations of ACh (10(-7) to 10(-6) mol/L). The contraction was endothelium-dependent and inhibited by indomethacin. 4. A23187-ind uced endothelium-dependent relaxations were also markedly attenuated i n the aorta and significantly in the coronary artery with age. 5. Endo thelium-independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages. 6. These finding s indicate that in the aorta and coronary artery of the WHHL rabbit, t he endothelium-dependent relaxation to ACh and A23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposi tion in the arterial wall) but is preserved in the basilar and renal a rtery.