期刊
JOURNAL OF HYPERTENSION
卷 36, 期 9, 页码 1902-1914出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000001762
关键词
angiotensin II type 1 receptor; AT1 blocker; neutroendopeptidase inhibitor; atrial natriuretic peptide; hypertension; neutroendopeptidase; stroke-prone spontaneously hypertensive rat; target organ damage
资金
- Italian Ministry of Health
- Novartis
Objectives:The combination of AT1 blocker/neutroendopeptidase neprilysin inhibition (ARNi) represents an interesting approach to reduce cardiovascular risk in hypertension. We assessed the efficacy of ARNi, compared with angiotensin II type 1 receptor blockade alone, on blood pressure (BP) and on protection from target organ damage development in the stroke-prone spontaneously hypertensive rat (SHRSP).Methods:In high-salt fed SHRSP, we assessed plasma and tissue natriuretic peptides, urinary volume, BP and body weight over a short-term treatment (6 weeks) with either ARNi (sacubitril/valsartan 68mg/kg per day) or valsartan (30mg/kg per day), protection from stroke and renal damage (as documented by proteinuria) over 4 months of treatment with either sacubitril/valsartan or valsartan; the ability of either treatment to reduce progression of cerebrovascular and renal damage after 2 weeks of high-salt diet.Results:Higher levels of plasma and tissue atrial natriuretic peptide, of urinary cyclic guanosine 35monophosphate and urine volumes, along with lower BP levels, were found upon sacubitril/valsartan as compared with valsartan over the short-term treatment. Sacubitril/valsartan caused a significant reduction of both BP and proteinuria levels and complete prevention of stroke over the long-term treatment. Once organ damage was established, a significant delay of its progression was observed with sacubitril/valsartan.Conclusion:The dual angiotensin II type 1 receptor/neutroendopeptidase inhibition significantly increased atrial natriuretic peptide level and reduced BP. Complete prevention of stroke was achieved in this model. The ability of sacubitril/valsartan to reduce organ damage progression was superior to that of valsartan alone. ARNi may represent a highly effective therapeutic agent to protect from target organ damage development in hypertension.
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