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


METHODS
Prospective trial.


METHODS
University laboratory.


METHODS
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.
Souza-Costa
Debora C
DC
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil.
Zerbini
Talita
T
Palei
Ana C
AC
Gerlach
Raquel F
RF
Tanus-Santos
Jose E
JE
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001120:Arginine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019331:NG-Nitroarginine Methyl Ester