Effect of metallothionein on tolerance of nitroglycerin in rats

AIM: To assess whether metallothionein (Met) could improve the nitroglyceri n tolerance in vivo; METHODS: Nitrate tolerance was induced by 2-d treatmen t of nitroglycerin (Nit) patch (0.05 mg.h(-1)). Endogenous Met production w as 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 p roduction was confirmed by the assay of liver and plasma Met levels. RESULT S: ZnCl2 induced large amount of endogenous Met production in liver and pla sma in Nit + ZnCl2 group than that in control group, (89+/-4) mu g/g tissue vs (11.0+/-2.4) mu g/ g tissue in liver, P < 0.01, and in plasma (85 +/- 6 ) mu g .L-1 vs (71+/-6) mu g.L-1, P < 0.01. There was no significant differ ence in plasma Met levels in Nit and control groups [(75 +/- 6) mu g.L-1 vs (71 +/- 6) mu g. L-1, P > 0.05]. The endogenous Met production enhanced th e 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 EC5 0(concentration which produces 50 % of the maximal response to SNP) was fou nd in tolerant group [(42 +/- 9) nmol.L-1, P < 0.01]. CONCLUSION: Exogenous Met or induction of endogenous Met production antagonize the development o f Nit tolerance.