RGD Reference Report - L-arginine attenuates acute pulmonary embolism-induced increases in lung matrix metalloproteinase-2 and matrix metalloproteinase-9. - Rat Genome Database

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L-arginine attenuates acute pulmonary embolism-induced increases in lung matrix metalloproteinase-2 and matrix metalloproteinase-9.

Authors: Souza-Costa, DC  Zerbini, T  Palei, AC  Gerlach, RF  Tanus-Santos, JE 
Citation: Souza-Costa DC, etal., Chest. 2005 Nov;128(5):3705-10.
RGD ID: 1582630
Pubmed: PMID:16304337   (View Abstract at PubMed)
DOI: DOI:10.1378/chest.128.5.3705   (Journal Full-text)

STUDY OBJECTIVES: To evaluate the effects of L-arginine on acute pulmonary embolism (APE)-induced pulmonary hypertension and increases in lung matrix metalloproteinase (MMP)-2 and MMP-9 activities. DESIGN: Prospective trial. SETTING: University laboratory. INTERVENTIONS: Using an isolated lung perfusion rat model of APE, we examined whether L-arginine (0, 0.5, 3, and 10 mmol/L; five to seven rats per group) attenuates the pulmonary hypertension induced by the injection of 6.6 mg/kg of 300 microm microspheres into the pulmonary artery. In a second series of experiments (6 to 11 rats per group), we investigated whether nonselective inhibition of nitric oxide (NO) synthases with N(G)-nitro-L-arginine methyl ester (L-NAME; 4 mmol/L) decreases the effects produced by L-arginine. Lung MMP-2 and MMP-9 activities were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis gelatin zymography. RESULTS: L-arginine at 0.5, 3, and 10 mmol/L attenuated APE-induced pulmonary hypertension by 25 to 42% (all p < 0.05). The protective effect of L-arginine was completely reversed by inhibition of NO synthesis with L-NAME. APE was associated with increased lung MMP-2 and MMP-9 activities (both p < 0.05). While L-arginine at 0.5 mmol/L produced no effect on MMPs, L-arginine 3 at mmol/L and 10 mmol/L attenuated the increases in MMP-2 and MMP-9 activities after APE (both p < 0.05). CONCLUSIONS: L-arginine attenuates APE-induced pulmonary hypertension through mechanisms involving increased NO synthesis and maybe attenuation of lung MMP-2 and MMP-9 activities.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Mmp2  (matrix metallopeptidase 2)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp2  (matrix metallopeptidase 2)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP2  (matrix metallopeptidase 2)
MMP9  (matrix metallopeptidase 9)


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