Beneficial effect of T-type calcium channel blockers on endothelial function in patients with essential hypertension.
Endothelial function is impaired in essential hypertension. T-type but not L-type voltage-gated Ca2+ channels were detected in the vascular endothelium. The purpose of the present study was to clarify the role of T-type Ca2+ channels in endothelial function. We studied flow-mediated vasodilation (FMD) and sublingual nitroglycerin (NTG)-induced vasodilation in the brachial artery. Forty patients with essential hypertension were randomly assigned to treatment with efonidipine, a T- and L-type Ca2+ channel blocker, or with nifedipine, an L-type Ca2+ channel blocker. Twenty healthy normotensive individuals were included as a control group. In patients with essential hypertension, FMD was attenuated and NTG was similar that of compared to healthy controls. After 12 weeks, the decrease in mean blood pressure in the efonidipine and nifedipine groups were similar. The endothelial function index, a ratio of FMD/NTG, was significantly increased by efonidipine (73 +/- 24 to 94 +/- 20%) but unchanged by nifedipine. Urinary excretion 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (LDL) were decreased by efonidipine but unchanged by nifedipine. These results suggest that a T-type Ca2+ channel blocker, but not an L-type Ca2+ channel blocker, may improve vascular endothelial dysfunction in patients with essential hypertension via a reduction in oxidative stress.
Department of Clinical Laboratory Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. teto@hiroshima-u.ac.jp
Tetsuya
T
Oshima
Ryoji
R
Ozono
Yoko
Y
Yano
Yukihito
Y
Higashi
Hiroki
H
Teragawa
Narimasa
N
Miho
Takafumi
T
Ishida
Mari
M
Ishida
Masao
M
Yoshizumi
Masayuki
M
Kambe
D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D009596:Nitrophenols / Q000494:pharmacology / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D009543:Nifedipine