Angiotensin II receptor antagonist improves age-related endothelial dysfunction

Yasuo Kansui, Koji Fujii, Kenichi Goto, Isao Abe, Mitsuo Iida

研究成果: ジャーナルへの寄稿記事

51 引用 (Scopus)

抄録

Background. We previously demonstrated that the angiotensin converting enzyme (ACE) inhibitor, enalapril, prevents the age-related impairment of endothelium-dependent hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF). Objective. To test whether angiotensin II type 1 (AT1) receptor antagonists would also improve age-related endothelial dysfunction. Methods. Normotensive Wistar-Kyoto (WKY) rats were treated for 3 months with either the AT1 receptor antagonist, candesartan cilexetil (3.5 mg/kg per day; candesartan group), or the ACE inhibitor, enalapril (20 mg/kg per day; enalapril group), from 9 to 12 months of age. Untreated 12-month-old WKY rats (old group) served as controls (n = 7-12). Results. The two treatments decreased systolic blood pressure comparably. EDHF-mediated hyperpolarization in response to acetylcholine (ACh; 10-5 mol/l) in the presence of norepinephrine in mesenteric arteries was improved in both the candesartan and enalapril groups to a similar extent compared with the old group (candesartan group, -24 ± 3 mV; enalapril group, -21 ± 2 mV; old group, -13 ± 2 mV). EDHF-mediated relaxation was similarly improved in the candesartan and enalapril groups (maximum relaxation: candesartan group, 70 ± 7%; enalapril group, 63 ± 8%; old group, 33 ± 9%). Hyperpolarization and relaxation responses to levcromakalim, an ATP-sensitive K+-channel opener, were similar in all groups. Conclusions. These findings suggest that the AT1 receptor antagonist is as effective as the ACE inhibitor in improving the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats. Thus AT1 receptor antagonists might serve as novel tools with which to prevent endothelial dysfunction associated with aging.

元の言語英語
ページ(範囲)439-446
ページ数8
ジャーナルJournal of Hypertension
20
発行部数3
DOI
出版物ステータス出版済み - 3 1 2002

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Enalapril
Angiotensin Receptor Antagonists
Angiotensin II Type 1 Receptor Blockers
Endothelium
Angiotensin-Converting Enzyme Inhibitors
Inbred WKY Rats
Cromakalim
Blood Pressure
Mesenteric Arteries
Acetylcholine
Norepinephrine
Adenosine Triphosphate
candesartan

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

これを引用

Angiotensin II receptor antagonist improves age-related endothelial dysfunction. / Kansui, Yasuo; Fujii, Koji; Goto, Kenichi; Abe, Isao; Iida, Mitsuo.

:: Journal of Hypertension, 巻 20, 番号 3, 01.03.2002, p. 439-446.

研究成果: ジャーナルへの寄稿記事

Kansui, Yasuo ; Fujii, Koji ; Goto, Kenichi ; Abe, Isao ; Iida, Mitsuo. / Angiotensin II receptor antagonist improves age-related endothelial dysfunction. :: Journal of Hypertension. 2002 ; 巻 20, 番号 3. pp. 439-446.
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abstract = "Background. We previously demonstrated that the angiotensin converting enzyme (ACE) inhibitor, enalapril, prevents the age-related impairment of endothelium-dependent hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF). Objective. To test whether angiotensin II type 1 (AT1) receptor antagonists would also improve age-related endothelial dysfunction. Methods. Normotensive Wistar-Kyoto (WKY) rats were treated for 3 months with either the AT1 receptor antagonist, candesartan cilexetil (3.5 mg/kg per day; candesartan group), or the ACE inhibitor, enalapril (20 mg/kg per day; enalapril group), from 9 to 12 months of age. Untreated 12-month-old WKY rats (old group) served as controls (n = 7-12). Results. The two treatments decreased systolic blood pressure comparably. EDHF-mediated hyperpolarization in response to acetylcholine (ACh; 10-5 mol/l) in the presence of norepinephrine in mesenteric arteries was improved in both the candesartan and enalapril groups to a similar extent compared with the old group (candesartan group, -24 ± 3 mV; enalapril group, -21 ± 2 mV; old group, -13 ± 2 mV). EDHF-mediated relaxation was similarly improved in the candesartan and enalapril groups (maximum relaxation: candesartan group, 70 ± 7{\%}; enalapril group, 63 ± 8{\%}; old group, 33 ± 9{\%}). Hyperpolarization and relaxation responses to levcromakalim, an ATP-sensitive K+-channel opener, were similar in all groups. Conclusions. These findings suggest that the AT1 receptor antagonist is as effective as the ACE inhibitor in improving the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats. Thus AT1 receptor antagonists might serve as novel tools with which to prevent endothelial dysfunction associated with aging.",
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