Evidence for Involvement of Calcitonin Gene-Related Peptide in Nitroglycerin Response and Association With Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism
Ren Guo, MD,
Xiao-Ping Chen, MD, PhD,
Xin Guo, MD,
Lei Chen, MS,
Dai Li, MD,
Jun Peng, MD, PhD and
Yuan-Jian Li, MD*
Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, Hunan, China
View larger version (21K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Change in Plasma CGRP After GTN Administration
Concentration of CGRP in plasma in each individual at baseline and 12 min after sublingual GTN administration was measured. Solid circles (n = 9) represent ALDH2*1/*1 homozygotes, open circles (n = 9) represent carriers of ALDH2*2 allele. CGRP = calcitonin gene-related peptide; other abbreviations as in Figure 1.
|
|
View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4 CGRP mRNA Expression After GTN Treatment
The expression of CGRP 1 and CGRP II messenger ribonucleic acid (mRNA) in cultured peripheral blood monuclear cells (PBMCs) in the presence of 10–5 mol/l GTN or not (control) for 24 h was studied. The CGRP I
(A) and CGRP II
(B) mRNA expression in PBMCs from ALDH2*1/*1 homozygotes (solid bars) and carriers of the ALDH2*2 allele (open bars) was analyzed by real-time polymerase chain reaction and expressed as percentage of control (mean ± SEM, n = 9, respectively). *p < 0.001 compared with carriers of the ALDH2*2 allele. GAPDH = glyceraldehyde-3-phosphate dehydrogenase; other abbreviations as in Figures 1 and 2.
|
|
View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5 CH Inhibited GTN-Induced CGRP Expression
Peripheral blood monuclear cells (PBMCs) from ALDH2*1/*1 homozygotes were seeded in the presence of GTN (10–5 mol/l) for 24 h with or without 1 mmol/l chloral hydrate (CH) pre-treatment (control group; GTN group: 10–5 mol/l GTN; GTN+CH group: 10–5 mol/l GTN+1 mmol/l CH; CH group: 1 mmol/l CH). The CGRP I and CGRP II mRNA expression in PBMCs was analyzed by real-time polymerase chain reaction and expressed as percentage of control (mean ± SEM, n = 3, respectively). *p < 0.05 compared with control. #p < 0.05 compared with corresponding GTN group. Abbreviations as in Figures 1, 2, and 4.
|
|
|
SBP) (D) and DBP (
