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Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP).
Int J Clin Pharmacol Ther. 2012 Oct; 50(10):701-11.IJ

Abstract

OBJECTIVE

The aim of this study was to investigate whether the neuropeptide calcitonin gene related peptide (CGRP) contributes to nitroglycerin (GTN) response in patients with chronic heart failure (CHF) and the association with the mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism.

METHODS

This is a 2-period, placebo-controlled clinical study. An intravenous infusion of saline followed by GTN (20 μg/min), each for 2 hours, respectively, was given to 49 stable CHF patients. Blood pressure (BP), heart rate (HR) and respiratory rate (RR) were measured at baseline, at 10 min, 30 min, 1.0 h, 1.5 h, and 2.0 h after initiation of saline infusion and initiation of GTN therapy. Blood samples were drawn for the determination of plasma CGRP for 49 patients at baseline, and at 2.0 h after initiation of saline and GTN infusion, respectively. Global clinical status of the patients was evaluated. Left ventricular ejection (LVEF), left ventricular end-diastolic volume (LVEDV), stroke volume (SV) and cardiac output (CO) were measured with 2D echocardiography with Simpson's biplane method (Pillip HP sonos 5500) by the same investigator at baseline and at 2.0 h after initiation of saline and GTN infusion.

RESULTS

Systolic blood pressure (SBP), diastolic blood pressure (DBP), and left ventricular end-diastolic volume (LVEDV) were decreased, while left ventricular ejection fraction (LVEF) was increased at the end of GTN infusion (p < 0.001, respectively). Saline infusion showed no hemodynamic effects. At the end of GTN infusion, ALDH2*1/*1 homozygous patients showed higher degrees of both the absolute decrease in SBP (DSBP) (p < 0.001) and increase in LVEF (p < 0.001) than carriers of the ALDH2*2 allele. Mean plasma concentration of CGRP was increased after GTN infusion (p < 0.001), but not changed after saline infusion (p > 0.05). Changes in plasma concentration of CGRP correlated positively with the improvement in LVEF (r = 0.400, p = 0.004), while correlated negatively with changes in SBP (r = -0.300, p = 0.036) and LVEDV (r = -0.290, p = 0.043).

CONCLUSIONS

ALDH2*2 polymorphism is associated with contributions of CGRP to GTN response in CHF patients.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, Hunan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22909898

Citation

Peng, Li-Ming, et al. "Influence of ALDH2 Glu504Lys Polymorphism On Nitroglycerin Response in Chronic Heart Failure and Involvement of Calcitonin Gene Related Peptide (CGRP)." International Journal of Clinical Pharmacology and Therapeutics, vol. 50, no. 10, 2012, pp. 701-11.
Peng LM, Chen XP, Sun J, et al. Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP). Int J Clin Pharmacol Ther. 2012;50(10):701-11.
Peng, L. M., Chen, X. P., Sun, J., Guo, Y. J., Li, L., Mo, L., Xie, W., Li, Y. J., Yang, T. L., & Li, C. C. (2012). Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP). International Journal of Clinical Pharmacology and Therapeutics, 50(10), 701-11. https://doi.org/10.5414/CP201635
Peng LM, et al. Influence of ALDH2 Glu504Lys Polymorphism On Nitroglycerin Response in Chronic Heart Failure and Involvement of Calcitonin Gene Related Peptide (CGRP). Int J Clin Pharmacol Ther. 2012;50(10):701-11. PubMed PMID: 22909898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP). AU - Peng,Li-Ming, AU - Chen,Xiao-Ping, AU - Sun,Ji, AU - Guo,Yi-Jie, AU - Li,Ling, AU - Mo,Long, AU - Xie,Wei, AU - Li,Yuan-Jian, AU - Yang,Tian-Lun, AU - Li,Chuan-Chang, PY - 2012/09/14/accepted PY - 2012/8/23/entrez PY - 2012/8/23/pubmed PY - 2012/11/14/medline SP - 701 EP - 11 JF - International journal of clinical pharmacology and therapeutics JO - Int J Clin Pharmacol Ther VL - 50 IS - 10 N2 - OBJECTIVE: The aim of this study was to investigate whether the neuropeptide calcitonin gene related peptide (CGRP) contributes to nitroglycerin (GTN) response in patients with chronic heart failure (CHF) and the association with the mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism. METHODS: This is a 2-period, placebo-controlled clinical study. An intravenous infusion of saline followed by GTN (20 μg/min), each for 2 hours, respectively, was given to 49 stable CHF patients. Blood pressure (BP), heart rate (HR) and respiratory rate (RR) were measured at baseline, at 10 min, 30 min, 1.0 h, 1.5 h, and 2.0 h after initiation of saline infusion and initiation of GTN therapy. Blood samples were drawn for the determination of plasma CGRP for 49 patients at baseline, and at 2.0 h after initiation of saline and GTN infusion, respectively. Global clinical status of the patients was evaluated. Left ventricular ejection (LVEF), left ventricular end-diastolic volume (LVEDV), stroke volume (SV) and cardiac output (CO) were measured with 2D echocardiography with Simpson's biplane method (Pillip HP sonos 5500) by the same investigator at baseline and at 2.0 h after initiation of saline and GTN infusion. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and left ventricular end-diastolic volume (LVEDV) were decreased, while left ventricular ejection fraction (LVEF) was increased at the end of GTN infusion (p < 0.001, respectively). Saline infusion showed no hemodynamic effects. At the end of GTN infusion, ALDH2*1/*1 homozygous patients showed higher degrees of both the absolute decrease in SBP (DSBP) (p < 0.001) and increase in LVEF (p < 0.001) than carriers of the ALDH2*2 allele. Mean plasma concentration of CGRP was increased after GTN infusion (p < 0.001), but not changed after saline infusion (p > 0.05). Changes in plasma concentration of CGRP correlated positively with the improvement in LVEF (r = 0.400, p = 0.004), while correlated negatively with changes in SBP (r = -0.300, p = 0.036) and LVEDV (r = -0.290, p = 0.043). CONCLUSIONS: ALDH2*2 polymorphism is associated with contributions of CGRP to GTN response in CHF patients. SN - 0946-1965 UR - https://www.unboundmedicine.com/medline/citation/22909898/Influence_of_ALDH2_Glu504Lys_polymorphism_on_nitroglycerin_response_in_chronic_heart_failure_and_involvement_of_Calcitonin_Gene_Related_Peptide__CGRP__ L2 - http://www.dustri.com/nc/journals-in-english.html?artId=9931 DB - PRIME DP - Unbound Medicine ER -