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 nitric oxide (NO)-synthase, nitro-L-arginine (L-NNA), in atherosclerotic aortas obtained from cholesterol-fed rabbits. In the atherosclerotic aortas, L-NNA (100 microM) caused endothelium-independent contractions that were not observed in aortas from control rabbits. L-NNA (100 microM) significantly 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 increases in the norepinephrine-induced contractions caused by L-NNA (1 to 100 microM) could be reversed by L-arginine (1 mM) both in atherosclerotic aortas with and without endothelium. L-NMMA also evoked concentration-dependent augmentations of the norepinephrine-induced contraction; the effect of L-NMMA was equipotent to that of L-NNA. Finally, L-NNA (100 microM) prevented the paradoxical endothelium-independent contraction to hypoxia in atherosclerotic aortas. These data strongly suggest that nonendothelial NO synthase has been induced in the aortas of the hyperlipidemic rabbit.
Verbeuren
T J
TJ
Institut de Recherches Servier, Division of Angiology, Suresnes, France.
Bonhomme
E
E
Laubie
M
M
Simonet
S
S
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D019323:omega-N-Methylarginine
D002791:Cholesterol, Dietary; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D012701:Serotonin; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009638:Norepinephrine