Tetrahydrobiopterin improves vascular endothelial function in ovariectomized rats.
The goal of the present study is to investigate the role of tetrahydrobiopterin (BH4) in the vascular response in ovariectomized rats. Rats were randomly assigned to two groups: (1) sham group: sham-operated female rats, and (2) Ovx group: rats were ovariectomized. Our results have shown that the plasma 17 beta-estradiol levels in the Ovx group at the end of the experiment were significantly lower than in the sham group. Vasoreactivity assessed with intact aortic rings indicated that the phenylephrine-induced vasocontractile response to aortic rings from the Ovx group was greater than that of the sham group. In contrast, the vasodilator responses to acetylcholine and L-arginine (L-Arg) in the sham group were significantly greater than in the Ovx group. Differences in vasoreactivity in denuded aorta between the two groups were not noted. Moreover, exogenous BH4 significantly restored L-Arg-induced vasodilator responses in the Ovx group. However, this improvement effect was not found in the sham group. In addition, there were significant increases in superoxide anion production in aortic tissue and significant decreases in plasma nitric oxide levels in the Ovx group. Furthermore, BH4 contents in the aorta in the Ovx group were significantly decreased compared with the sham group. In conclusion, the present study demonstrates that the impairment of vascular reactivity was found in the ovariectomized rats. The possible mechanism of this defect may have resulted from the deficiency of available BH4. Thus, this study may provide a novel therapeutic strategy for the treatment of postmenopausal cardiovascular disorders.
Lam
Kwok-Keung
KK
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Ho
Shung-Tai
ST
Yen
Mao-Hsiung
MH
D000818:Animals; D001011:Aorta; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000097:blood / Q000172:deficiency / Q000502:physiology; D005260:Female; D017942:Nitric Acid / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D013481:Superoxides; D010656:Phenylephrine; D001708:Biopterins; D017942:Nitric Acid; D004958:Estradiol; C003402:sapropterin