Induction of a calcium-independent NO synthase by hypercholesterolaemia in the rabbit

Endothelium-dependent and -independent relaxation of aortic ring preparations was assessed and nitric oxide (NO) synthase activity measured in the lung, and cerebellum of cholesterol-fed and normal rabbits. Endothelium-dependent relaxation of acetylcholine and ATP was depressed while that to the calcium ionophore, A23187, was unaltered in the cholesterol-fed group. Relaxation to sodium nitroprusside was however greater in aortae from the cholesterol-fed animals. Neither Ca(2+)-dependent nor Ca(2+)-independent NO synthase activity could be detected in aortae or hearts taken from either group of animals. Activity of both enzymes was unaltered in cerebellae from both groups of animals. Activity of the Ca(2+)-independent enzyme was however significantly greater (ca. 2 fold) in lungs from the cholesterol-fed rabbits though the activity of the Ca(2+)-dependent NO synthase was not significantly altered. This finding may account for the increased production of nitrogen oxides previously observed in this model of hypercholesterolaemia.