title: LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone.
abstract: BACKGROUND
  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.
  
  
  METHODS
  (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.
  
  
  RESULTS
  (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kusaka
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sueta
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: BoWen
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; mitsuyam@gpo.kumamoto-u.ac.jp.
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D002940:Circadian Rhythm / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D009206:Myocardium / Q000473:pathology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000009:adverse effects / Q000652:urine; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000068756:Valsartan / Q000494:pharmacology / Q000627:therapeutic use*; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D012982:Sodium, Dietary; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; D006152:Cyclic GMP; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: angiotensin; blood pressure; cardiovascular protection; dual inhibition; hypertension; neprilysin.