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Updated: Jul 14, 2026
07:59
Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration
Published on: April 4, 2022
Decrease in endogenous CGRP release in nitroglycerin tolerance: role of ALDH-2
Yue-Rong Chen1, Sheng-Dan Nie, Wang Shan
1Department of Pharmacology, School of Pharmaceautical Sciences, Central South University, Changsha 410078, China.
European Journal of Pharmacology
|June 26, 2007
Summary
Nitrate tolerance involves reduced calcitonin gene-related peptide (CGRP) release, linked to decreased aldehyde dehydrogenase-2 (ALDH-2) activity. Reactive oxygen species contribute to this reduction, impacting vasodilator responses.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Biochemistry
Background:
- Nitroglycerin tolerance is a clinical challenge affecting therapeutic efficacy.
- Reduced calcitonin gene-related peptide (CGRP) release is implicated in nitroglycerin tolerance.
- Aldehyde dehydrogenase-2 (ALDH-2) plays a role in cardiovascular homeostasis.
Purpose of the Study:
- To investigate the association between decreased CGRP release and reduced ALDH-2 activity in nitroglycerin tolerance.
- To explore the role of reactive oxygen species (ROS) in the diminished ALDH-2 activity during nitroglycerin tolerance.
- To assess the impact of ALDH-2 inhibition and ROS modulation on nitroglycerin's effects.
Main Methods:
- Induction of nitroglycerin tolerance in isolated rat thoracic aortas and human umbilical vein endothelial cells (HUVEC) in vitro and in vivo.
- Assessment of vasodilator responses, CGRP release, ALDH-2 activity, and reactive oxygen species production.
- Pharmacological interventions using ALDH-2 inhibitors, N-acetylcysteine, and captopril.
Main Results:
- Nitroglycerin tolerance was associated with decreased CGRP release and reduced ALDH-2 activity.
- Exposure to nitroglycerin increased ROS production and decreased ALDH-2 and cGMP levels in HUVEC.
- ALDH-2 inhibition attenuated nitroglycerin's vasodilator and depressor effects, and CGRP release.
- N-acetylcysteine and captopril restored tolerance in HUVEC, suggesting ROS involvement.
Conclusions:
- Nitrate tolerance is partly mediated by decreased endogenous CGRP release.
- Reduced ALDH-2 activity, driven by increased ROS production, contributes to nitrate tolerance.
- Targeting ALDH-2 or ROS may offer strategies to overcome nitroglycerin tolerance.
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