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Effect of metallothionein on tolerance of nitroglycerin in rats
1Department of Pediatrics, First Hospital, Beijing Medical University, Beijing 100034, China.
Aim:
To assess whether metallothionein (Met) could improve the nitroglycerin tolerance in vivo.
Methods:
Nitrate tolerance was induced by 2-d treatment of nitroglycerin (Nit) patch (0.05 mg.h-1). Endogenous Met production was induced by pretreatment of ZnCl2 and coadministration of intravenous Met (15 mg.kg-1.d-1) 2 d with Nit in tolerant rats. The induction of Met production was confirmed by the assay of liver and plasma Met levels.
Results:
ZnCl2 induced large amount of endogenous Met production in liver and plasma in Nit + ZnCl2 group than that in control group, (89 +/- 4) micrograms/g tissue vs (11.0 +/- 2.4) micrograms/g tissue in liver, P < 0.01, and in plasma (85 +/- 6) micrograms.L-1 vs (71 +/- 6) micrograms.L-1, P < 0.01. There was no significant difference in plasma Met levels in Nit and control groups [(75 +/- 6) micrograms.L-1 vs (71 +/- 6) micrograms.L-1, P > 0.05]. The endogenous Met production enhanced the hypotensive response in Nit + ZnCl2 group [(15.7 +/- 0.8) kPa vs (11.5 +/- 0.6) kPa, n = 6, P < 0.05]. The maximal vessel relaxation induced by sodium nitroprusside (SNP) was the same in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response to SNP) was found in tolerant group [(42 +/- 9) nmol.L-1, P < 0.01].
Conclusion:
Exogenous Met or induction of endogenous Met production antagonize the development of Nit tolerance.