1. Three analogues of L-arginine were characterized as inhibitors endothelial nitric oxide (NO) synthase by measuring their effect on the NO from porcine aortae, vascular tone rings rat aorta and blood pressure anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO) NG-nitro-L-arginine methyl ester (L-NAME; all at 0.1-100 microM) caused concentration-dependent inhibition Ca2(+)-dependent aortae. 3. L-NMMA, L-NIO L-NAME an endothelium-dependent contraction...

The role of endothelium-derived nitric oxide in the regulation blood pressure anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not D-enantiomer, induced dose-dependent long-lasting (15-90 min) increase mean systemic arterial pressure. (100 mg.kg-1) also inhibited significantly hypotensive action acetylcholine, without affecting that glyceryl trinitrate. Both these actions were reversed...

A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline L-arginine. The NO formed stimulates guanylate cyclase this stimulation is abolished by low concentrations hemoglobin. synthesis dependent on presence physiological free Ca2+ inhibited NG-monomethyl-L-arginine, but not its enantiomer NG-monomethyl-D-arginine or L-canavanine. L-Homoarginine, L-arginyl-L-aspartate, L-arginine methyl ester can replace as substrates for...

Aggregation of human washed platelets with collagen is accompanied by a concentration-dependent increase in cyclic GMP but not AMP. NG-Monomethyl-L-arginine (L-MeArg), selective inhibitor nitric oxide (NO) synthesis from L-arginine, reduces this and enhances aggregation. L-Arginine, which has no effect on the basal levels GMP, augments nucleotide induced also inhibits Both these effects L-arginine are attenuated L-MeArg. The anti-aggregatory action potentiated prostacyclin M&B22948,...

1 The interactions between endothelium-derived nitric oxide (NO) and prostacyclin as inhibitors of platelet aggregation were examined. 2 Porcine aortic endothelial cells treated with indomethacin stimulated bradykinin (10–100 nm) released NO in quantities sufficient to account for the inhibition attributed relaxing factor (EDRF). 3 In absence indomethacin, stimulation (1–3 small amounts EDRF which synergistically inhibited aggregation. 4 authentic also caused disaggregation platelets...

Vascular endothelial cells contain a constitutive nitric oxide (NO) synthase that is Ca2(+)-dependent. In addition, we have found these express, after activation with interferon-gamma and lipopolysaccharide, an inducible Ca2(+)-independent NO distinct from the enzyme. The generation of by this enzyme was detectable lag period 2 hr, reached maximum between 6 12 maintained for duration experiment (48 hr). expression inhibited protein synthesis inhibitor cycloheximide, compound had no direct...

The role of l ‐arginine in the basal and stimulated generation nitric oxide (NO) for endothelium‐dependent relaxation was studied by use N G ‐monomethyl ( ‐NMMA), a specific inhibitor this pathway. ‐Arginine (10–100 μ m ), but not d (100 induced small significant relaxations rings rabbit aorta. In contrast, ‐NMMA (1–300 ) produced small, contractions, while its enantiomer ‐monomethyl‐ (d‐NMMA; 100 μ) had no effect. inhibited acetylcholine (ACh), calcium ionophore A23187, substance P or...

The pharmacological effects of endothelium‐derived relaxing factor (EDRF), nitric oxide (NO) and prostacyclin on human rabbit platelets were examined. EDRF is released from porcine aortic endothelial cells, cultured microcarriers treated with indomethacin, in sufficient quantities to inhibit platelet aggregation induced by 9,11‐dideoxy‐9α,11α‐methano epoxy‐prostaglandin F 2α (U46619) collagen. anti‐aggregating activity was potentiated M&B 22948, a selective inhibitor cyclic GMP...

Peritoneal macrophages from CBA mice incubated with rIFN-gamma are effective in killing the protozoal parasite Leishmania major vitro. This leishmanicidal activity can be completely inhibited by L-NG-monomethyl arginine (L-NMMA), a specific inhibitor of L-arginine:nitric oxide (NO) pathway. The culture supernatants macrophage activated IFN-gamma contain increased levels NO2-, production which is L-NMMA, but not its D-enantiomer. L. promastigotes killed when at room temperature PBS containing...

Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for in inflammatory processes. Nitric production was therefore measured indirectly as nitrite serum synovial fluid samples from patients with rheumatoid arthritis (RA) osteoarthritis (OA) together healthy volunteers matched age sex. Serum concentrations RA OA were significantly higher than controls. In both disease groups nitrite, implying the synovium. also those OA....

Stimulated rat peritoneal neutrophils release a platelet inhibitory factor with the pharmacological properties of NO. This is inhibited by NG-monomethyl-L-arginine and L-canavanine, indicating that it occurs through mechanism similar to in vascular endothelial cells macrophages. As degree stimulation increases, released progressively inactivated concomitant superoxide anions.

The mechanism of the increased sensitivity to nitrovasodilators after removal endothelial nitric oxide (NO) was investigated in vitro and vivo. vasoconstrictor potency phenylephrine force contraction rat isolated aortic rings were significantly enhanced endothelium or treatment with inhibitors NO synthase. Furthermore, these procedures led a significant decrease basal levels cGMP vascular rings. Moreover, glyceryl trinitrate (n3Gro) sodium nitroprusside (SNP) as relaxing agents ability SNP...