Effect of glutathione peroxidase mimic ebselen (PZ51) on endothelium and vascular structure of stroke-prone spontaneously hypertensive rats.
BACKGROUND
To investigate whether extrinsic antioxidant seleno-glutathione peroxidase mimic ebselen (PZ51) can protect endothelium and vascular structure of stroke-prone spontaneously hypertensive rats (SHRsp) during the chronic process of hypertension.


METHODS
Twenty-two 8-week-old SHRsp were randomized into a PZ51 group and a control group, and administered by gavage for 6 weeks. We examined the level of nitric oxide (NO) and malonaldehyde (MDA) in plasma. The intima-media thickness (IMT) of the common carotid artery (CCA) was measured by an image-analysis system. The endothelium of the CCA was observed by scanning electron microscopy. The eNOS protein of the major artery was assayed by immunohistochemistry and western blotting.


RESULTS
Compared with the control group, PZ51 decreased plasma MDA (7.88+/-1.06 vs 10.88+/-1.73 nmol/l, p<0.001) and increased plasma NO (40.02+/-9.74 vs 22.22+/-10.05 micromol/l, p<0.001), increased eNOS protein expression (8.25+/-2.36 vs 4.46+/-3.14, p=0.026), decreased IMT (69.85+/-5.47 vs 76.60+/-6.53 microm, p<0.05) significantly and alleviated the damage to the endothelium of the CCA.


CONCLUSIONS
Administration of PZ51 for 6 weeks can protect the endothelium and inhibit vascular remodeling, maybe due to its suppression of lipid peroxide formation and increase in eNOS protein expression.
Sui
Hui
H
Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Wang
Wen
W
Wang
Pei-He
PH
Liu
Li-Sheng
LS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D007150:Immunohistochemistry; D054833:Isoindoles; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D009569:Nitric Oxide; C042986:ebselen; D008315:Malondialdehyde; D052250:Nitric Oxide Synthase Type III