Kusaka Hiroaki, Sueta Daisuke, Koibuchi Nobutaka, Hasegawa Yu, Nakagawa Takashi, Lin BoWen, Ogawa Hisao, Kim-Mitsuyama Shokei
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Am J Hypertens. 2015 Dec;28(12):1409-17. doi: 10.1093/ajh/hpv015. Epub 2015 Mar 10.
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.
(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.
(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.
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.
血管紧张素受体脑啡肽酶抑制剂LCZ696最近被证明对高血压或心力衰竭患者比传统的肾素-血管紧张素系统阻滞剂具有更多有益作用。然而，LCZ696有益作用的潜在机制仍有待了解。本研究旨在探讨与缬沙坦相比，LCZ696对高血压和心血管损伤的影响。
（i）使用遥测技术，我们比较了LCZ696和缬沙坦在高盐饮食后改为低盐饮食的自发性高血压大鼠（SHR）中的降压效果。（ii）我们还研究了LCZ696和缬沙坦对盐负荷SHRcp（一种代谢综合征模型）的比较作用。
（i）无论高盐或低盐摄入，LCZ696在SHR中比缬沙坦具有更大的血压降低作用。LCZ696的额外血压降低与尿钠排泄显著增加和交感神经活动抑制有关。（ii）与缬沙坦相比，LCZ696显著改善了高盐负荷SHRcp中的心脏肥大和炎症、冠状动脉重塑以及血管内皮功能障碍。
无论盐摄入程度如何，LCZ696在SHR中引起的血压降低比缬沙坦更大，这与尿钠排泄显著增加和交感神经活动抑制有关。此外，LCZ696的额外降压作用导致高血压大鼠获得更大的心血管保护。
