Effects of dual angiotensin type 1 receptor/neprilysin inhibition vs. angiotensin type 1 receptor inhibition on target organ injury in the stroke-prone spontaneously hypertensive rat

Research output: Contribution to journalArticle

Abstract

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 3050monophosphate 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.

Original languageEnglish
Pages (from-to)1902-1914
Number of pages13
JournalJournal of Hypertension
Volume36
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

Keywords

  • Angiotensin II type 1 receptor
  • AT1 blocker/ neutroendopeptidase inhibitor
  • Atrial natriuretic peptide
  • Hypertension
  • Neutroendopeptidase
  • Stroke-prone spontaneously hypertensive rat
  • Target organ damage

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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