Effects of the antioxidative beta-blocker celiprolol on endothelial progenitor cells in hypertensive rats.
BACKGROUND
Endothelial progenitor cells (EPCs) derived from bone marrow migrate to areas of endothelial damage and repair them. EPC function is impaired by oxidative stress. We examined the effects of an antioxidative beta1-adrenoceptor blocker on the number and function of EPCs in hypertensive rats.


METHODS
Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were fed diets loaded with high salt. The SHRs were treated with celiprolol or atenolol for 2 weeks. Peripheral blood mononuclear cells (MNCs) were separated, subjected to flow cytometric analysis to determine the number of circulating EPCs, and cultured to quantify EPC colony formation. EPC migration was evaluated in migration assay chambers. EPC senescence was evaluated using beta-galactosidase assay. Oxidative stress of EPCs was evaluated using thiobarbituric acid-reactive substance (TBARS) assay. The expression of nicotinamine adenine dinucleotide phosphate (NAD(P)H) oxidase component mRNAs in the renal cortex, aorta, and heart were evaluated by real-time PCR.


RESULTS
The number, colony formation, and migration of EPCs in SHRs were significantly lower than those in WKY rats. TBARS scores in EPCs from SHRs were significantly higher than those from WKY rats. Celiprolol increased the number of circulating EPCs and stimulated EPC colony formation and migration, while decreasing EPC senescence. Celiprolol inhibited oxidation in EPCs from SHRs, and decreased the expression of NAD(P)H oxidase component mRNAs in the renal cortex, aorta, and heart.


CONCLUSIONS
EPCs are impaired in SHRs in response to oxidative stress. Celiprolol decreases oxidative stress in hypertension in vivo and improves EPC numbers and function. It appears, therefore, that celiprolol may exert beneficial cardiovascular effects through its antioxidative properties.
Yao
En-Hui
EH
Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Fukuda
Noboru
N
Matsumoto
Taro
T
Katakawa
Mayumi
M
Yamamoto
Chii
C
Han
Ying
Y
Ueno
Takahiro
T
Kobayashi
Naohiko
N
Matsumoto
Koichi
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017272:Celiprolol / Q000494:pharmacology*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D019255:NADPH Oxidases / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013234:Stem Cells / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D012333:RNA, Messenger; D017272:Celiprolol; D019255:NADPH Oxidases