Enalapril and losartan affect lipid peroxidation in renal transplant recipients with renin-angiotensin system polymorphisms.
OBJECTIVE
In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin-angiotensin system (RAS).


METHODS
After determination of genotypes of the angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E(+): 10 mg/day) and losartan (L(+): 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril+losartan (E(+)L(+): 10 mg/day+50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E(-)L(-)). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P<0.05 was considered significant.


RESULTS
After 2 months of treatment, MDA level significantly decreased in all of the groups except the E(-)L(-). MDA level in pre- vs. post-intervention for the E(+)L(+), E(+), L(+) and E(-)L(-) groups were as follows: 5.81+/-2.13 nmol/mL vs. 1.61+/-0.80 nmol/mL (P=0.001), 5.10+/-2.05 nmol/mL vs. 1.68+/-1.01 nmol/mL (P=0.003), 5.20+/-1.61 nmol/mL vs. 1.22+/-0.27 nmol/mL (P=0.000) and 5.27+/-2.12 nmol/mL vs. 5.07+/-2.03 nmol/mL (P=0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA (P=0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs (P>0.05).


CONCLUSIONS
E and/or L reduce MDA regardless of the RAS genotypes.
Rashtchizadeh
Nadereh
N
Drug Applied Research Center (DARC), Biotechnology Research Center, Tabriz Medical University, Tabriz, Iran. rashtchizadeh@yahoo.com
Aghaeishahsavari
Mohammad
M
Argani
Hassan
H
Noroozianavval
Masood
M
Veisi
Pegah
P
Ghorbanihaghjo
Amir
A
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000808:Angiotensinogen / Q000235:genetics; D018592:Cross-Over Studies; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D015227:Lipid Peroxidation / Q000187:drug effects*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D017422:Sequence Analysis, DNA
D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D008315:Malondialdehyde; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan