Renin-angiotensin system blockade improves endothelial dysfunction in hypertension

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

69 引用 (Scopus)

抄録

Angiotensin-converting enzyme (ACE) inhibitor improves the impaired hyperpolarization and relaxation to acetylcholine (ACh) via endothelium-derived hyperpolarizing factor (EDHF) in arteries of spontaneously hypertensive rats (SHR). We tested whether the angiotensin type 1 (AT1) receptor antagonist also improves EDHF-mediated responses and whether the combined AT1 receptor blockade and ACE inhibition exert any additional effects. SHR were treated with either AT1 receptor antagonist TCV-116 (5 mg · kg-1 · d-1) (SHR-T), enalapril (40 mg · kg-1 · d-1) (SHR-E), or their combination (SHR-TandE) from 8 to 11 months of age. Age-matched, untreated SHR (SHR-C) and Wistar Kyoto (WKY) rats served as controls (n=8 to 12 in each group). Three treatments lowered blood pressure comparably. EDHF-mediated hyperpolarization to ACh in mesenteric arteries in the absence or presence of norepinephrine was significantly improved in all treated SHR. In addition, the hyperpolarization in the presence of norepinephrine was significantly greater in SHR-TandE than in SHR-E (ACh 10-5 mol/L with norepinephrine: SHR-C -7; SHR-T -19; SHR-E -15; SHR-TandE -22; WKY -14 mV). EDHF-mediated relaxation, assessed in the presence of indomethacin and N(G)-nitro-L-arginine, was markedly improved in all treated SHR. Hyperpolarization and relaxation to levcromakalim, a direct opener of ATP-sensitive K+-channel, were similar in all groups. These findings suggest that AT1 receptor antagonists are as effective as ACE inhibitors in improving EDHF-mediated responses in SHR. The beneficial effects of the combined AT1 receptor blockade and ACE inhibition appears to be for the most part similar to those of each intervention.

元の言語英語
ページ(範囲)575-580
ページ数6
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 SHR Rats
Renin-Angiotensin System
Hypertension
Endothelium
Angiotensin II Type 1 Receptor Blockers
Acetylcholine
Norepinephrine
Angiotensin Type 1 Receptor
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme Inhibitors
Cromakalim
Enalapril
Mesenteric Arteries
Inbred WKY Rats
Indomethacin
Arginine

All Science Journal Classification (ASJC) codes

  • Internal Medicine

これを引用

Renin-angiotensin system blockade improves endothelial dysfunction in hypertension. / Goto, Kenichi; Fujii, Koji; Onaka, Uran; Abe, Isao; Fujishima, Masatoshi.

:: Hypertension, 巻 36, 番号 4, 01.01.2000, p. 575-580.

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. / Renin-angiotensin system blockade improves endothelial dysfunction in hypertension. :: Hypertension. 2000 ; 巻 36, 番号 4. pp. 575-580.
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N2 - Angiotensin-converting enzyme (ACE) inhibitor improves the impaired hyperpolarization and relaxation to acetylcholine (ACh) via endothelium-derived hyperpolarizing factor (EDHF) in arteries of spontaneously hypertensive rats (SHR). We tested whether the angiotensin type 1 (AT1) receptor antagonist also improves EDHF-mediated responses and whether the combined AT1 receptor blockade and ACE inhibition exert any additional effects. SHR were treated with either AT1 receptor antagonist TCV-116 (5 mg · kg-1 · d-1) (SHR-T), enalapril (40 mg · kg-1 · d-1) (SHR-E), or their combination (SHR-TandE) from 8 to 11 months of age. Age-matched, untreated SHR (SHR-C) and Wistar Kyoto (WKY) rats served as controls (n=8 to 12 in each group). Three treatments lowered blood pressure comparably. EDHF-mediated hyperpolarization to ACh in mesenteric arteries in the absence or presence of norepinephrine was significantly improved in all treated SHR. In addition, the hyperpolarization in the presence of norepinephrine was significantly greater in SHR-TandE than in SHR-E (ACh 10-5 mol/L with norepinephrine: SHR-C -7; SHR-T -19; SHR-E -15; SHR-TandE -22; WKY -14 mV). EDHF-mediated relaxation, assessed in the presence of indomethacin and N(G)-nitro-L-arginine, was markedly improved in all treated SHR. Hyperpolarization and relaxation to levcromakalim, a direct opener of ATP-sensitive K+-channel, were similar in all groups. These findings suggest that AT1 receptor antagonists are as effective as ACE inhibitors in improving EDHF-mediated responses in SHR. The beneficial effects of the combined AT1 receptor blockade and ACE inhibition appears to be for the most part similar to those of each intervention.

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