Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats

Kwok Keung Lam, Yen Mei Lee, George Hsiao, Shu Ying Chen, Mao Hsiung Yen

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objective: We investigated whether the effect of estrogen therapy on vascular endothelial function is mediated through increasing the bioavailability of tetrahydrobiopterin (BH4) and associated antioxidant capacity in ovariectomized (Ovx) rats. Design: Aortas of sham-operated, Ovx, and Ovx plus estrogen therapy (Ovx + ET) female Sprague-Dawley rats were used to measure vascular reactivity. Plasma levels of nitric oxide (NO) metabolites, total antioxidant capacity, aortic superoxide anion (O2.-, and BH4 contents were determined. Results: Vascular reactivity, assessed on isolated aortic segments, indicated that phenylephrine-induced contraction in the Ovx group was significantly greater than that in the sham and Ovx + ET groups. The vasodilator responses to acetylcholine (10-9 to 10 -5 M) and L-arginine (L-Arg; 10-4 M) in the sham and Ovx + ET groups were significantly greater than those in the Ovx group. Pretreatment with BH4 (10-5 M) enhanced the vasodilator responses to L-Arg in the Ovx group compared with the untreated Ovx group. An inhibitor of BH4 synthesis, 2,4-diamino-6-hydroxypyrimidine (2 mM), significantly attenuated the vasodilator response to L-Arg in the sham and Ovx + ET groups. In addition, Ovx significantly increased O2.- production in aortic tissues and decreased plasma NO metabolites levels, whereas ET significantly prevented these effects. Pretreatment with BH4 also significantly decreased aortic O2.- production in the Ovx group; both plasma total antioxidant capacity and aortic BH4 contents in the Ovx group decreased significantly compared with those in the sham group, which were also improved by ET. There were no significant differences in the protein expression of endothelial NO synthase in aortas in these groups. Conclusions: ET increases the availability of vascular BH4 to attenuate O2.- production and restores total antioxidant capacity, leading to improved NO-mediated vasodilation in Ovx rats.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalMenopause
Volume13
Issue number2
DOIs
Publication statusPublished - Mar 2006

Fingerprint

Blood Vessels
Estrogens
Oxidative Stress
Antioxidants
Vasodilator Agents
Nitric Oxide
Aorta
Nitric Oxide Synthase Type III
Phenylephrine
Therapeutics
Vasodilation
Superoxides
Biological Availability
Acetylcholine
Sprague Dawley Rats
Arginine
sapropterin
Proteins

Keywords

  • 17β-Estradiol
  • Nitric oxide
  • Ovariectomy
  • Superoxide anion
  • Tetrahydrobiopterin
  • Vascular reactivity

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats. / Lam, Kwok Keung; Lee, Yen Mei; Hsiao, George; Chen, Shu Ying; Yen, Mao Hsiung.

In: Menopause, Vol. 13, No. 2, 03.2006, p. 294-302.

Research output: Contribution to journalArticle

Lam, Kwok Keung ; Lee, Yen Mei ; Hsiao, George ; Chen, Shu Ying ; Yen, Mao Hsiung. / Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats. In: Menopause. 2006 ; Vol. 13, No. 2. pp. 294-302.
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abstract = "Objective: We investigated whether the effect of estrogen therapy on vascular endothelial function is mediated through increasing the bioavailability of tetrahydrobiopterin (BH4) and associated antioxidant capacity in ovariectomized (Ovx) rats. Design: Aortas of sham-operated, Ovx, and Ovx plus estrogen therapy (Ovx + ET) female Sprague-Dawley rats were used to measure vascular reactivity. Plasma levels of nitric oxide (NO) metabolites, total antioxidant capacity, aortic superoxide anion (O2.-, and BH4 contents were determined. Results: Vascular reactivity, assessed on isolated aortic segments, indicated that phenylephrine-induced contraction in the Ovx group was significantly greater than that in the sham and Ovx + ET groups. The vasodilator responses to acetylcholine (10-9 to 10 -5 M) and L-arginine (L-Arg; 10-4 M) in the sham and Ovx + ET groups were significantly greater than those in the Ovx group. Pretreatment with BH4 (10-5 M) enhanced the vasodilator responses to L-Arg in the Ovx group compared with the untreated Ovx group. An inhibitor of BH4 synthesis, 2,4-diamino-6-hydroxypyrimidine (2 mM), significantly attenuated the vasodilator response to L-Arg in the sham and Ovx + ET groups. In addition, Ovx significantly increased O2.- production in aortic tissues and decreased plasma NO metabolites levels, whereas ET significantly prevented these effects. Pretreatment with BH4 also significantly decreased aortic O2.- production in the Ovx group; both plasma total antioxidant capacity and aortic BH4 contents in the Ovx group decreased significantly compared with those in the sham group, which were also improved by ET. There were no significant differences in the protein expression of endothelial NO synthase in aortas in these groups. Conclusions: ET increases the availability of vascular BH4 to attenuate O2.- production and restores total antioxidant capacity, leading to improved NO-mediated vasodilation in Ovx rats.",
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T1 - Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats

AU - Lam, Kwok Keung

AU - Lee, Yen Mei

AU - Hsiao, George

AU - Chen, Shu Ying

AU - Yen, Mao Hsiung

PY - 2006/3

Y1 - 2006/3

N2 - Objective: We investigated whether the effect of estrogen therapy on vascular endothelial function is mediated through increasing the bioavailability of tetrahydrobiopterin (BH4) and associated antioxidant capacity in ovariectomized (Ovx) rats. Design: Aortas of sham-operated, Ovx, and Ovx plus estrogen therapy (Ovx + ET) female Sprague-Dawley rats were used to measure vascular reactivity. Plasma levels of nitric oxide (NO) metabolites, total antioxidant capacity, aortic superoxide anion (O2.-, and BH4 contents were determined. Results: Vascular reactivity, assessed on isolated aortic segments, indicated that phenylephrine-induced contraction in the Ovx group was significantly greater than that in the sham and Ovx + ET groups. The vasodilator responses to acetylcholine (10-9 to 10 -5 M) and L-arginine (L-Arg; 10-4 M) in the sham and Ovx + ET groups were significantly greater than those in the Ovx group. Pretreatment with BH4 (10-5 M) enhanced the vasodilator responses to L-Arg in the Ovx group compared with the untreated Ovx group. An inhibitor of BH4 synthesis, 2,4-diamino-6-hydroxypyrimidine (2 mM), significantly attenuated the vasodilator response to L-Arg in the sham and Ovx + ET groups. In addition, Ovx significantly increased O2.- production in aortic tissues and decreased plasma NO metabolites levels, whereas ET significantly prevented these effects. Pretreatment with BH4 also significantly decreased aortic O2.- production in the Ovx group; both plasma total antioxidant capacity and aortic BH4 contents in the Ovx group decreased significantly compared with those in the sham group, which were also improved by ET. There were no significant differences in the protein expression of endothelial NO synthase in aortas in these groups. Conclusions: ET increases the availability of vascular BH4 to attenuate O2.- production and restores total antioxidant capacity, leading to improved NO-mediated vasodilation in Ovx rats.

AB - Objective: We investigated whether the effect of estrogen therapy on vascular endothelial function is mediated through increasing the bioavailability of tetrahydrobiopterin (BH4) and associated antioxidant capacity in ovariectomized (Ovx) rats. Design: Aortas of sham-operated, Ovx, and Ovx plus estrogen therapy (Ovx + ET) female Sprague-Dawley rats were used to measure vascular reactivity. Plasma levels of nitric oxide (NO) metabolites, total antioxidant capacity, aortic superoxide anion (O2.-, and BH4 contents were determined. Results: Vascular reactivity, assessed on isolated aortic segments, indicated that phenylephrine-induced contraction in the Ovx group was significantly greater than that in the sham and Ovx + ET groups. The vasodilator responses to acetylcholine (10-9 to 10 -5 M) and L-arginine (L-Arg; 10-4 M) in the sham and Ovx + ET groups were significantly greater than those in the Ovx group. Pretreatment with BH4 (10-5 M) enhanced the vasodilator responses to L-Arg in the Ovx group compared with the untreated Ovx group. An inhibitor of BH4 synthesis, 2,4-diamino-6-hydroxypyrimidine (2 mM), significantly attenuated the vasodilator response to L-Arg in the sham and Ovx + ET groups. In addition, Ovx significantly increased O2.- production in aortic tissues and decreased plasma NO metabolites levels, whereas ET significantly prevented these effects. Pretreatment with BH4 also significantly decreased aortic O2.- production in the Ovx group; both plasma total antioxidant capacity and aortic BH4 contents in the Ovx group decreased significantly compared with those in the sham group, which were also improved by ET. There were no significant differences in the protein expression of endothelial NO synthase in aortas in these groups. Conclusions: ET increases the availability of vascular BH4 to attenuate O2.- production and restores total antioxidant capacity, leading to improved NO-mediated vasodilation in Ovx rats.

KW - 17β-Estradiol

KW - Nitric oxide

KW - Ovariectomy

KW - Superoxide anion

KW - Tetrahydrobiopterin

KW - Vascular reactivity

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