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 ldehyde 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.

Author Details

Authors

• Li-Ming Peng¹,²
• Xiao-Ping Chen¹
• Ji Sun¹
• Yi-Jie Guo¹
• Ling Li¹
• Long Mo²
• Wei Xie²
• Yuan-Jian Li¹
• Tian-Lun Yang²
• Chuan-Chang Li²

Departments

• ¹ Department of Pharmacology, School of Pharmaceutical Science, and
• ² Xiangya Hospital, Central South University, Changsha, Hunan, China

Address

Xiao-Ping Chen, PhD
Department of Pharmacology
School of Pharmaceutical Science
Central South University
Changsha, Hunan 410078, China

or
Chuan-Chang Li, MD
Department of cardiology,
Xiangya hospital,
Central South University,
Changsha, Hunan 410078, China
Email: [email protected], [email protected]

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