Sacubitril , Valsartan Used For Heart Failure.

How it works

Sacubitril + valsartan inhibits neprilysin (neutral endopeptidase; NEP) , the active metabolite of the prodrug sacubitril and blocks the angiotensin II type-1 (AT1) receptor via valsartan. The cardiovascular and renal effects of sacubitril + valsartan in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides (NPs) and the simultaneous inhibition of the effects of angiotensin II by valsartan. NPs exert their effects by activating membrane bound guanylyl cyclase coupled receptors, resulting in increased concentrations of the second messenger cyclic guanosine monophosphate (cGMP), which could result in vasodilation, natriuresis and diuresis, increased glomerular filtration rate and renal blood flow, inhibition of renin and aldosterone release, reduction ofsympathetic activity and antihypertrophic and antifibrotic effects. Valsartan inhibits the effects of angiotensin II by selectively blocking the AT1 receptor and also inhibits angiotensin II-dependent aldosterone release. This prevents sustained activation of the renin-angiotensin-aldosterone system that would result in vasoconstriction, renal sodium and fluid retention, activation of cellular growth and proliferation and subsequent maladaptive cardiovascular remodeling.