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. Issue 9 (September 2018)

• Record Type: Journal Article
• Authors: Rubattu, Speranza; Cotugno, Maria; Forte, Maurizio; Stanzione, Rosita; Bianchi, Franca; Madonna, Michele; Marchitti, Simona; Volpe, Massimo
• Is Part Of: Journal of hypertension. Volume 36:Issue 9(2018:Sep.)
• Publication Date: 2018-09
• Subjects: angiotensin II type 1 receptor -- AT1 blocker/neutroendopeptidase inhibitor -- atrial natriuretic peptide -- hypertension -- neutroendopeptidase -- stroke-prone spontaneously hypertensive rat -- target organ damage; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000001762
• Languages: English
• ISSNs: 1473-5598

Abstract

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 68 mg/kg per day) or valsartan (30 mg/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.