EVIDENCE FOR INDUCTION OF NONENDOTHELIAL NO SYNTHASE IN AORTAS OF CHOLESTEROL-FED RABBITS

The aim of our study was to examine the effects of the inhibitor of ni tric oxide (NO)-synthase, nitro-L-arginine (L-NNA), in atherosclerotic aortas obtained from cholesterol-fed rabbits. In the atherosclerotic aortas, L-NNA (100 muM) caused endothelium-independent contractions th at were not observed in aortas from control rabbits. L-NNA (100 muM) s ignificantly enhanced the contractile responses to norepinephrine and 5-hydroxytryptamine (5-HT) in atherosclerotic aortas with and without endothelium; in control aortas, L-NNA only augmented the response to 5 -HT when the endothelium was present. The concentration-dependent incr eases in the norepinephrine-induced contractions caused by L-NNA (1 to 100 muM) could be reversed by L-arginine (1 mM) both in atherosclerot ic aortas with and without endothelium. L-NMMA also evoked concentrati on-dependent augmentations of the norepinephrine-induced contraction; the effect Of L-NMMA was equipotent to that of L-NNA. Finally, L-NNA ( 100 muM) prevented the paradoxical endothelium-independent contraction to hypoxia in atherosclerotic aortas. These data strongly suggest tha t nonendothelial NO synthase has been induced in the aortas of the hyp erlipidemic rabbit.