Angiotensin-converting enzyme inhibitor prevents age-related endothelial dysfunction

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

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63 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)581-587
Number of pages7
Issue number4
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Internal Medicine


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