Influence of SIN-1 and sodium nitroprusside (NANP) on ox-LDL metabolism in macrophages.
Effects of NO-donors (3-morpholinosydnonimine-SIN-1 and sodium nitroprusside NaNP) on the accumulation and degradation of oxidized LDL (ox-LDL) by macrophages were studied. Ox-LDL, but not native-LDL (n-LDL) suppressed the LPS-stimulated biosynthesis of NO by macrophages. SIN-1 at low concentrations < 100 microM was without any effect while SIN-1 at high concentration (300 microM) and NaNP (30-300 microM) stimulated the accumulation and degradation of ox-LDL by macrophages. The pretreatment of macrophages with NG-monomethyl-L-arginine (L-NMMA, 3 microM) for 24 hours had the same stimulatory effect. The inhibition of endogenous formation of NO, by L-NMMA profoundly changed the pattern of action of NO-donors on ox-LDL catabolism by macrophages; the stimulatory action of SIN-1 was transformed to the inhibitory action on the accumulation and degradation of ox-LDL whereas NaNP lost its stimulatory action entirely. Our interpretation of this unexpected interactions between SIN-1, NaNP and L-NMMA is as follows. Endogenous NO in macrophages inhibits the accumulation of ox-LDL and therefore, the stimulatory effect of L-NMMA has been overcome by exogenous NO from SIN-1. However, NO at high concentrations promotes lipid accumulation in macrophages and thereby, in the absence of L-NMMA, SIN-1 at high concentrations and NaNP produced a paradoxical stimulatory effect in macrophages. NaNP is not a proper NO-donor and its mode of action differed from that of SIN-1. In conclusion, NO at low physiological concentrations keeps scavenger receptors of macrophages downregulated and hence endogenous NO may show anti-atherogenic properties.
Department of Clinical Biochemistry, Collegium Medicum Jagiellonian University, Cracow, Poland.
I
I
Wybrańska
B
B
Miszczuk-Jamska
E
E
Baczyńska
P
P
Goldsztajn
G
G
Sowa
R
R
Przewłocki
R
R
Gryglewski
A
A
Dembińska-Kieć
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D008077:Lipoproteins, LDL; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine