Effect of nebivolol and metoprolol treatments on serum asymmetric dimethylarginine levels in hypertensive patients with type 2 diabetes mellitus.
OBJECTIVE
Elevated asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric oxide synthase, are an important cardiovascular risk factor. In patients with diabetes, increased ADMA levels have been reported, which may be associated with endothelial dysfunction. In this study, effect of nebivolol on serum ADMA levels in hypertensive patients with type 2 diabetes have been compared with metoprolol, an another beta-blocker.


METHODS
A total of 54 patients (27 female, 27 male; mean age: 53.0+/-8.7 years) with type 2 diabetes and hypertension were included in this randomized, open-label, prospective study. Patients were randomized to receive either nebivolol 5 mg/day (n=28) or metoprolol 100 mg/day (n=26) for 12 weeks. When the patients could not reach target blood pressure levels at the end of week 4, indapamide (2.5 mg/day) was added. Enzyme Linked Immunosorbent Assay was used for serum ADMA measurements.


RESULTS
Similar reductions in blood pressure values were observed in both groups (p>0.05). In nebivolol group, there were no significant changes in serum ADMA levels compared to baseline (0.6+/-0.2 micromol/l vs 0.6+/-0.1 micromol/l, p>0.05), whereas in metoprolol group a 35.6% increase in serum ADMA levels was observed (0.6+/-0.1 micromol/l vs 0.7+/-0.2 micromol/l, p<0.01).


CONCLUSIONS
We observed a significant increase in ADMA levels, a marker of endothelial dysfunction, during metoprolol treatment, whereas nebivolol had neutral effects on ADMA levels in patients with type 2 diabetes mellitus and hypertension.
Department of Internal Medicine, Göztepe Training and Research Hospital, Istanbul, Turkey.
Aytekin
A
Oğuz
Mehmet
M
Uzunlulu
Elif
E
Yorulmaz
Yavuz
Y
Yalçin
Nezih
N
Hekim
Francesco
F
Fici
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001578:Benzopyrans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D000068577:Nebivolol; D011446:Prospective Studies; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D015415:Biomarkers; D004983:Ethanolamines; D014280:Triglycerides; C487735:dimethylarginine; D000068577:Nebivolol; D001120:Arginine; D008790:Metoprolol