TY - JOUR
T1 - Neutral endopeptidase inhibition and the natriuretic peptide system
T2 - An evolving strategy in cardiovascular therapeutics
AU - Mangiafico, Sarah
AU - Costello-Boerrigter, Lisa C.
AU - Andersen, Ingrid A.
AU - Cataliotti, Alessandro
AU - Burnett, John C.
N1 - Funding Information:
Supported by grants from the National Institutes of Health: HL R01 36634, HL P01 76611, HL R01 098502-01A1, and the Mayo Foundation, Rochester, MN, USA.
PY - 2013/3/21
Y1 - 2013/3/21
N2 - Hypertension and heart failure (HF) are common diseases that, despite advances in medical therapy, continue to be associated with high morbidity and mortality. Therefore, innovative therapeutic strategies are needed. Inhibition of the neutral endopeptidase (NEPinh) had been investigated as a potential novel therapeutic approach because of its ability to increase the plasma concentrations of the natriuretic peptides (NPs). Indeed, the NPs have potent natriuretic and vasodilator properties, inhibit the activity of the renin-angiotensin-aldosterone system, lower sympathetic drive, and have antiproliferative and antihypertrophic effects. Such potentially beneficial effects can be theoretically achieved by the use of NEPinh. However, studies have shown that NEPinh alone does not result in clinically meaningful blood pressure-lowering actions. More recently, NEPinh has been used in combination with other cardiovascular agents, such as angiotensin-converting enzyme inhibitors, and antagonists of the angiotensin receptor. Another future possible combination would be the use of NEPinh with NPs or their newly developed chimeric peptides. This review summarizes the current knowledge of the use and effects of NEPinh alone or in combination with other therapeutic agents for the treatment of human cardiovascular disease such as HF and hypertension. All rights reserved.
AB - Hypertension and heart failure (HF) are common diseases that, despite advances in medical therapy, continue to be associated with high morbidity and mortality. Therefore, innovative therapeutic strategies are needed. Inhibition of the neutral endopeptidase (NEPinh) had been investigated as a potential novel therapeutic approach because of its ability to increase the plasma concentrations of the natriuretic peptides (NPs). Indeed, the NPs have potent natriuretic and vasodilator properties, inhibit the activity of the renin-angiotensin-aldosterone system, lower sympathetic drive, and have antiproliferative and antihypertrophic effects. Such potentially beneficial effects can be theoretically achieved by the use of NEPinh. However, studies have shown that NEPinh alone does not result in clinically meaningful blood pressure-lowering actions. More recently, NEPinh has been used in combination with other cardiovascular agents, such as angiotensin-converting enzyme inhibitors, and antagonists of the angiotensin receptor. Another future possible combination would be the use of NEPinh with NPs or their newly developed chimeric peptides. This review summarizes the current knowledge of the use and effects of NEPinh alone or in combination with other therapeutic agents for the treatment of human cardiovascular disease such as HF and hypertension. All rights reserved.
KW - Evolving strategy in cardiovascular therapeutics
KW - Natriuretic peptide system
KW - Neutral endopeptidase inhibition
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U2 - 10.1093/eurheartj/ehs262
DO - 10.1093/eurheartj/ehs262
M3 - Review article
C2 - 22942338
AN - SCOPUS:84875580118
SN - 0195-668X
VL - 34
SP - 886
EP - 893
JO - European heart journal
JF - European heart journal
IS - 12
ER -