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.
J Hypertens
; 36(9): 1902-1914, 2018 09.
Article
in En
| MEDLINE
| ID: mdl-29916993
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 68âmg/kg per day) or valsartan (30âmg/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 3'5'monophosphate 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tetrazoles
/
Stroke
/
Angiotensin II Type 1 Receptor Blockers
/
Valsartan
/
Aminobutyrates
/
Hypertension
/
Antihypertensive Agents
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Hypertens
Year:
2018
Document type:
Article