{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:52:40Z","timestamp":1790142760748,"version":"4.0.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T00:00:00Z","timestamp":1425945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>LCZ696, an angiotensin receptor-neprilysin inhibitor, has recently been demonstrated to exert more beneficial effects on hypertensive or heart failure patients than conventional renin-angiotensin system blockers. However, the mechanism underlying the benefit of LCZ696 remains to be understood. The present study was undertaken to examine the effect of LCZ696 compared with valsartan on hypertension and cardiovascular injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>(i) Using telemetry, we compared the hypotensive effect of LCZ696 and valsartan in spontaneously hypertensive rats (SHR) that were fed a high-salt diet followed by a low-salt diet. (ii) We also examined the comparative effect of LCZ696 and valsartan on salt loaded SHRcp, a model of metabolic syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>(i) LCZ696 exerted a greater blood pressure (BP) lowering effect than valsartan in SHR regardless of high-salt or low-salt intake. Additive BP reduction by LCZ696 was associated with a significant increase in urinary sodium excretion and sympathetic activity suppression. (ii) LCZ696 significantly ameliorated cardiac hypertrophy and inflammation, coronary arterial remodeling, and vascular endothelial dysfunction in high-salt loaded SHRcp compared with valsartan.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>LCZ696 caused greater BP reduction than valsartan in SHR regardless of the degree of salt intake, which was associated with a significant enhancement in urinary sodium excretion and sympathetic activity suppression. Furthermore, an additive BP lowering effect of LCZ696 led to greater cardiovascular protection in hypertensive rats.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpv015","type":"journal-article","created":{"date-parts":[[2015,3,12]],"date-time":"2015-03-12T00:32:09Z","timestamp":1426120329000},"page":"1409-1417","source":"Crossref","is-referenced-by-count":66,"title":["LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone"],"prefix":"10.1093","volume":"28","author":[{"given":"Hiroaki","family":"Kusaka","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sueta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Koibuchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BoWen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences 2 , Kumamoto , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shokei","family":"Kim-Mitsuyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences 1 , Kumamoto , Japan ;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"2023120820525723800_CIT0001","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1161\/01.HYP.0000054215.71691.16","article-title":"Vasopeptidase inhibition: a double-edged sword?","volume":"41","author":"Campbell","year":"2003","journal-title":"Hypertension"},{"key":"2023120820525723800_CIT0002","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1161\/CIRCHEARTFAILURE.112.000289","article-title":"Renin-angiotensin blockade combined with natriuretic peptide system augmentation: novel therapeutic concepts to combat heart failure","volume":"6","author":"von Lueder","year":"2013","journal-title":"Circ Heart Fail"},{"key":"2023120820525723800_CIT0003","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1097\/00004872-199207000-00002","article-title":"Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension","volume":"10","author":"Bevan","year":"1992","journal-title":"J Hypertens"},{"key":"2023120820525723800_CIT0004","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(05)77712-6","article-title":"Lack of efficacy of neutral endopeptidase inhibitor ecadotril in heart failure. 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