{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:46:49Z","timestamp":1793134009351,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,10,11]]},"abstract":"\n Background<\/jats:title>\n \n We have previously demonstrated that antihypertensive treatment with renin\u2010angiotensin system inhibitors restores the impaired endothelium\u2010dependent hyperpolarization (\n EDH<\/jats:styled-content>\n )\u2013mediated responses in spontaneously hypertensive rats (\n SHR<\/jats:styled-content>\n s). Herein, we investigated whether the angiotensin\n II<\/jats:styled-content>\n receptor\u2013neprilysin inhibitor sacubitril\/valsartan (\n LCZ<\/jats:styled-content>\n 696) would improve reduced\n EDH<\/jats:styled-content>\n \u2010mediated responses and whether\n LCZ<\/jats:styled-content>\n 696 would exert additional effects on endothelium\u2010dependent and endothelium\u2010independent vasorelaxation compared with an angiotensin\n II<\/jats:styled-content>\n type 1 receptor blocker alone during hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n SHR<\/jats:styled-content>\n s were treated for 3\u00a0months with either\n LCZ<\/jats:styled-content>\n 696 or valsartan, from the age of 8 to 11\u00a0months. Age\u2010matched, untreated\n SHR<\/jats:styled-content>\n s and Wistar\u2010Kyoto rats served as controls. Membrane potentials and contractile responses were recorded from the isolated superior mesenteric arteries. Acetylcholine\u2010induced,\n EDH<\/jats:styled-content>\n \u2010mediated responses were impaired in untreated\n SHR<\/jats:styled-content>\n s compared with Wistar\u2010Kyoto rats.\n EDH<\/jats:styled-content>\n \u2010mediated responses were similarly improved in the\n LCZ<\/jats:styled-content>\n 696\u2010 and valsartan\u2010treated\n SHR<\/jats:styled-content>\n s. No difference was observed in acetylcholine\u2010induced, nitric oxide\u2010mediated relaxations among the 4 groups. Endothelium\u2010independent relaxations in response to a nitric oxide donor, sodium nitroprusside, and those to levcromakalim, an\n ATP<\/jats:styled-content>\n \u2010sensitive K\n +<\/jats:sup>\n \u2010channel opener, were similar among the 4 groups; however, the sensitivities to levcromakalim were significantly higher in both\n LCZ<\/jats:styled-content>\n 696\u2010 and valsartan\u2010treated\n SHR<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n LCZ<\/jats:styled-content>\n 696 appears to be as effective as valsartan in improving the impaired\n EDH<\/jats:styled-content>\n \u2010mediated responses during hypertension.\n LCZ<\/jats:styled-content>\n 696 and valsartan exert similar beneficial effects on endothelium\u2010independent relaxation via enhanced sensitivity of the\n ATP<\/jats:styled-content>\n \u2010sensitive K\n +<\/jats:sup>\n channel. However, the dual blockade of renin\u2010angiotensin system and neutral endopeptidase with\n LCZ<\/jats:styled-content>\n 696 does not appear to provide additional benefit over valsartan alone on vasomotor function in mesenteric arteries of\n SHR<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.006617","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T00:10:20Z","timestamp":1508285420000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Angiotensin II Receptor\u2013Neprilysin Inhibitor Sacubitril\/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"6","author":[{"given":"Takunori","family":"Seki","sequence":"first","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Kansui","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Ohtsubo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, 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