Angiotensin-converting enzyme inhibitor prevents age-related endothelial dysfunction

Kenichi Goto, Koji Fujii, Uran Onaka, Isao Abe, Masatoshi Fujishima

研究成果: ジャーナルへの寄稿記事

60 引用 (Scopus)

抄録

Vascular relaxation via endothelium-derived hyperpolarizing factor (EDHF) declines in association with aging and also with hypertension, and antihypertensive treatment improves the endothelial dysfunction connected with hypertension. We tested whether the angiotensin-converting enzyme inhibitor improves EDHF-mediated responses in normotensive rats, with special reference to the age-related process. Wistar-Kyoto rats (WKY) were treated with either 20 mg · kg-1 · d-1 enalapril (WKY-E group) or a combination of 50 mg · kg-1 · d-1 hydralazine and 7.5 mg · kg-1 · d-1 hydrochlorothiazide (WKY-H group) from 9 to 12 months of age. Twelve-month-old WKY (WKY-O) and 3-month-old WKY (WKY-Y) served as controls (n = 6 to 10 in each group). The 2 treatments lowered systolic blood pressure comparably. EDHF-mediated hyperpolarization to acetylcholine (ACh) in mesenteric arteries was significantly improved in WKY-E, but not in WKY-H, compared with WKY-O, and the hyperpolarization in WKY-E was comparable to that in WKY-Y (hyperpolarization to 10-5 mol/L ACh in the presence of norepinephrine: WKY-O, -14±2 mV; WKY-E, -22±3 mV; WKY-H, -15±2 mV; and WKY-Y, -28±0 mV). EDHF-mediated relaxation, as assessed by relaxation to ACh in norepinephrine-precontracted tings in the presence of indomethacin and NO synthase inhibitor, was also significantly improved in WKY-E, but not in WKY-H, to a level comparable to that in WKY-Y (maximum relaxation: WKY-O, 45±6%; WKY-E, 63±8%; WKY-H, 43±4%; and WKY-Y, 72±4%). Hyperpolarization and relaxation to levcromakalim, an ATP-sensitive K+ channel opener, were similar in all groups. These findings suggest that the angiotensin-converting enzyme inhibitor prevents the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats, presumably through an inhibition of the renin-angiotensin system.

元の言語英語
ページ(範囲)581-587
ページ数7
ジャーナルHypertension
36
発行部数4
DOI
出版物ステータス出版済み - 1 1 2000

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Inbred WKY Rats
Angiotensin-Converting Enzyme Inhibitors
Endothelium
Acetylcholine
Norepinephrine
Tolnaftate
Cromakalim
Blood Pressure
Hypertension

All Science Journal Classification (ASJC) codes

  • Internal Medicine

これを引用

Angiotensin-converting enzyme inhibitor prevents age-related endothelial dysfunction. / Goto, Kenichi; Fujii, Koji; Onaka, Uran; Abe, Isao; Fujishima, Masatoshi.

:: Hypertension, 巻 36, 番号 4, 01.01.2000, p. 581-587.

研究成果: ジャーナルへの寄稿記事

Goto, Kenichi ; Fujii, Koji ; Onaka, Uran ; Abe, Isao ; Fujishima, Masatoshi. / Angiotensin-converting enzyme inhibitor prevents age-related endothelial dysfunction. :: Hypertension. 2000 ; 巻 36, 番号 4. pp. 581-587.
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abstract = "Vascular relaxation via endothelium-derived hyperpolarizing factor (EDHF) declines in association with aging and also with hypertension, and antihypertensive treatment improves the endothelial dysfunction connected with hypertension. We tested whether the angiotensin-converting enzyme inhibitor improves EDHF-mediated responses in normotensive rats, with special reference to the age-related process. Wistar-Kyoto rats (WKY) were treated with either 20 mg · kg-1 · d-1 enalapril (WKY-E group) or a combination of 50 mg · kg-1 · d-1 hydralazine and 7.5 mg · kg-1 · d-1 hydrochlorothiazide (WKY-H group) from 9 to 12 months of age. Twelve-month-old WKY (WKY-O) and 3-month-old WKY (WKY-Y) served as controls (n = 6 to 10 in each group). The 2 treatments lowered systolic blood pressure comparably. EDHF-mediated hyperpolarization to acetylcholine (ACh) in mesenteric arteries was significantly improved in WKY-E, but not in WKY-H, compared with WKY-O, and the hyperpolarization in WKY-E was comparable to that in WKY-Y (hyperpolarization to 10-5 mol/L ACh in the presence of norepinephrine: WKY-O, -14±2 mV; WKY-E, -22±3 mV; WKY-H, -15±2 mV; and WKY-Y, -28±0 mV). EDHF-mediated relaxation, as assessed by relaxation to ACh in norepinephrine-precontracted tings in the presence of indomethacin and NO synthase inhibitor, was also significantly improved in WKY-E, but not in WKY-H, to a level comparable to that in WKY-Y (maximum relaxation: WKY-O, 45±6{\%}; WKY-E, 63±8{\%}; WKY-H, 43±4{\%}; and WKY-Y, 72±4{\%}). Hyperpolarization and relaxation to levcromakalim, an ATP-sensitive K+ channel opener, were similar in all groups. These findings suggest that the angiotensin-converting enzyme inhibitor prevents the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats, presumably through an inhibition of the renin-angiotensin system.",
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N2 - Vascular relaxation via endothelium-derived hyperpolarizing factor (EDHF) declines in association with aging and also with hypertension, and antihypertensive treatment improves the endothelial dysfunction connected with hypertension. We tested whether the angiotensin-converting enzyme inhibitor improves EDHF-mediated responses in normotensive rats, with special reference to the age-related process. Wistar-Kyoto rats (WKY) were treated with either 20 mg · kg-1 · d-1 enalapril (WKY-E group) or a combination of 50 mg · kg-1 · d-1 hydralazine and 7.5 mg · kg-1 · d-1 hydrochlorothiazide (WKY-H group) from 9 to 12 months of age. Twelve-month-old WKY (WKY-O) and 3-month-old WKY (WKY-Y) served as controls (n = 6 to 10 in each group). The 2 treatments lowered systolic blood pressure comparably. EDHF-mediated hyperpolarization to acetylcholine (ACh) in mesenteric arteries was significantly improved in WKY-E, but not in WKY-H, compared with WKY-O, and the hyperpolarization in WKY-E was comparable to that in WKY-Y (hyperpolarization to 10-5 mol/L ACh in the presence of norepinephrine: WKY-O, -14±2 mV; WKY-E, -22±3 mV; WKY-H, -15±2 mV; and WKY-Y, -28±0 mV). EDHF-mediated relaxation, as assessed by relaxation to ACh in norepinephrine-precontracted tings in the presence of indomethacin and NO synthase inhibitor, was also significantly improved in WKY-E, but not in WKY-H, to a level comparable to that in WKY-Y (maximum relaxation: WKY-O, 45±6%; WKY-E, 63±8%; WKY-H, 43±4%; and WKY-Y, 72±4%). Hyperpolarization and relaxation to levcromakalim, an ATP-sensitive K+ channel opener, were similar in all groups. These findings suggest that the angiotensin-converting enzyme inhibitor prevents the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats, presumably through an inhibition of the renin-angiotensin system.

AB - Vascular relaxation via endothelium-derived hyperpolarizing factor (EDHF) declines in association with aging and also with hypertension, and antihypertensive treatment improves the endothelial dysfunction connected with hypertension. We tested whether the angiotensin-converting enzyme inhibitor improves EDHF-mediated responses in normotensive rats, with special reference to the age-related process. Wistar-Kyoto rats (WKY) were treated with either 20 mg · kg-1 · d-1 enalapril (WKY-E group) or a combination of 50 mg · kg-1 · d-1 hydralazine and 7.5 mg · kg-1 · d-1 hydrochlorothiazide (WKY-H group) from 9 to 12 months of age. Twelve-month-old WKY (WKY-O) and 3-month-old WKY (WKY-Y) served as controls (n = 6 to 10 in each group). The 2 treatments lowered systolic blood pressure comparably. EDHF-mediated hyperpolarization to acetylcholine (ACh) in mesenteric arteries was significantly improved in WKY-E, but not in WKY-H, compared with WKY-O, and the hyperpolarization in WKY-E was comparable to that in WKY-Y (hyperpolarization to 10-5 mol/L ACh in the presence of norepinephrine: WKY-O, -14±2 mV; WKY-E, -22±3 mV; WKY-H, -15±2 mV; and WKY-Y, -28±0 mV). EDHF-mediated relaxation, as assessed by relaxation to ACh in norepinephrine-precontracted tings in the presence of indomethacin and NO synthase inhibitor, was also significantly improved in WKY-E, but not in WKY-H, to a level comparable to that in WKY-Y (maximum relaxation: WKY-O, 45±6%; WKY-E, 63±8%; WKY-H, 43±4%; and WKY-Y, 72±4%). Hyperpolarization and relaxation to levcromakalim, an ATP-sensitive K+ channel opener, were similar in all groups. These findings suggest that the angiotensin-converting enzyme inhibitor prevents the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats, presumably through an inhibition of the renin-angiotensin system.

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