{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:58:16Z","timestamp":1791219496951,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2000,10]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Vascular 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 \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7  d\n            <jats:sup>\u22121<\/jats:sup>\n            enalapril (WKY-E group) or a combination of 50 mg  \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 d\n            <jats:sup>\u22121<\/jats:sup>\n            hydralazine and  7.5 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 d\n            <jats:sup>\u22121<\/jats:sup>\n            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\n            <jats:sup>\u2212<\/jats:sup>\n            <jats:sup>5<\/jats:sup>\n            mol\/L ACh in the presence of  norepinephrine: WKY-O, \u221214\u00b12 mV; WKY-E, \u221222\u00b13 mV;  WKY-H, \u221215\u00b12 mV; and WKY-Y, \u221228\u00b10 mV). EDHF-mediated relaxation, as  assessed by relaxation to ACh in  norepinephrine-precontracted rings 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\u00b16%; WKY-E,  63\u00b18%; WKY-H, 43\u00b14%; and WKY-Y, 72\u00b14%).  Hyperpolarization and relaxation to levcromakalim,  an ATP-sensitive K\n            <jats:sup>+<\/jats:sup>\n            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.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.36.4.581","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"581-587","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Angiotensin-Converting Enzyme Inhibitor Prevents Age-Related Endothelial Dysfunction"],"prefix":"10.1161","volume":"36","author":[{"given":"Kenichi","family":"Goto","sequence":"first","affiliation":[{"name":"From the Department of Medicine and Clinical Science, Graduate School of  Medical Sciences, Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fujii","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Clinical Science, Graduate School of  Medical Sciences, Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uran","family":"Onaka","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Clinical Science, Graduate School of  Medical Sciences, Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Abe","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Clinical Science, Graduate School of  Medical Sciences, Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Fujishima","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and Clinical Science, Graduate School of  Medical Sciences, Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.65.1.2544316"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb10306.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb11752.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.11.3337"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017522"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.65.1.2786773"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.70.4.1551193"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.78.3.415"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/46816"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/24388"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.505ae.x"},{"key":"e_1_3_2_12_2","first-page":"H509","volume":"265","year":"1993","unstructured":"Fujii K, Ohmori S, Tominaga M, Abe I, Takata Y, Ohya Y, Kobayashi K, Fujishima M. 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