Comparing The Role Of Glutathione -S- Transferase And Mitochondrial Aldehyde Dehydrogenase In Nitroglycerin Biotransformation And The Correlation With Calcitonin Gene-related Peptide

Both glutathione S - transferase(GSTs) and mitochondrial aldehyde dehydrogenase(ALDH-2) have been reported to participate in the biotransformation of nitroglycerin.In this study,we explored which is the major player in nitroglycerin biotransformation.Methods:In vivo,rats was treated with nitroglycerin,the blood pressure and plasma CGRP were measured.The inhibitor of GSTs (ethacrynic acid) or ALDH-2(cyanamide) was given before nitroglycerin treatment;In vitro,the isolated aorta rings were incubated with nitroglycerin to obtain the concentration - response curve.Ethacrynic acid or cyanamide was pre-incubated with the rings before nitroglycerin treatment.The release of CGRP from the aorta rings was determined.Results:Both ethacrynic acid and cyanamide were able to reverse the depressant action of nitroglycerin while the inhibitory effect of cyanamide was more profound.However,combined administration of ethacrynic acid and cyanamide did not produce an additive effect.The change of plasma CGRP level positively correlated with the change of nitroglycerin - induced hypotensive effects.In the isolated aorta rings, vasodilator responses to nitroglycerin were reduced in the presence of ethacrynic acid or cyanamide while the inhibitory effect of cyanamide was more profound.However,combined administration of both ethacrynic acid and cyanamide did not produce an additive effect.The change of CGRP release from the rings positively correlated with the nitroglycerin - induced vasodilator responses.Conclusion:The present results suggest that both GSTs and ALDH-2 are involved in nitroglycerin action while ALDH-2 plays a major role,and the change of CGRP contents closely correlates with thebiotransformation of nitroglycerin.