New insights into nitroglycerin effects and tolerance: role of calcitonin gene-related peptide.

It has been shown that calcitonin gene-relate peptide plays an extensive role in cardiovascular system. CGRP is a potent vasodilator and plays an important role in mediation of nitroglycerin-induced vascular relaxation. Recently, calcitonin gene-relate peptide is emerging as a potential player in nitroglycerin tolerance. There is increasing evidence that the decreased depressor effect of nitroglycerin in tolerant states is closely related to a decrease in calcitonin gene-relate peptide release. The reduced release of calcitonin gene-relate peptide in nitroglycerin tolerance is associated with the decreased nitroglycerin biotransformation due to the mitochondrial dysfunction. Recent work has been shown that the inhibited activity of mitochondrial isoform of aldehyde dehydrogenase and the upregulation of phosphodiesterase 1A1 are the key factors that lead to the decreased nitroglycerin biotransformation in nitroglycerin tolerance, with a subsequently reduced release of calcitonin gene-relate peptide.