The Role of Neuroendocrine Abnormalities in the Enhanced Sodium and Water Retention of Chronic Heart Failure

McMurray, John J.; Struthers, Allan D.

doi:10.1111/j.1600-0773.1987.tb01805.x

Cited by 6 publications

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References 58 publications

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“…hypertrophy and fibrosis) in heart failure . Conceptually, such an approach is complementary to inhibition of the detrimental antinatriuretic, vasoconstrictor, and pathological growth‐promoting systems (such as the renin–angiotensin–aldosterone and sympathetic nervous systems), a strategy that has proved marvellously successful and which forms the fundamental basis of the current pharmacological therapy for heart failure with reduced left ventricular ejection fraction (HF‐REF) ( Figure ) . Of course, as we have learnt from other neurohumoral therapeutic strategies, most notably use of endothelin receptor antagonists, the reality may be very different from the theory …”

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Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances

McMurray

2015

European J of Heart Fail

116

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This review describes the role of neprilysin (also known as neutral endopeptidase or enkephalinase) in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin. The initial development of neprilysin inhibitors, then angiotensin converting enzyme‐neprilysin inhibitors and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment of heart failure is also summarised. Finally, the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF) is discussed.

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confidence: 99%

Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances

McMurray

2015

European J of Heart Fail

116

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Diuretics

McMurray¹,

McEwen²

1990

Early Phase Drug Evaluation in Man

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Frusemide pretreatment blunts the inhibition of renal tubular sodium reabsorption by ANF in man

McMurray

Struthers

1988

Eur J Clin Pharmacol

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The effects of atrial natriuretic factor (ANF) 15 pmol/kg/min on renal function were studied in 7 normal male volunteers during maximal water diuresis. Subjects were studied in neutral salt balance either before, or after, seven days treatment with 40 mg oral frusemide. The post-frusemide state was associated with activation of the renin-angiotensin system (RAAS) and generally higher noradrenaline levels; this state was also associated with sodium retention, mainly due to enhanced distal nephron reabsorption. Without diuretic pretreatment ANF produced a natriuresis and diuresis associated with inhibition of both proximal and distal nephron sodium reabsorption. In contrast, after frusemide pretreatment, ANF caused an increase in water excretion (urinary flow rate) but no change in sodium excretion. In the post-diuretic condition ANF did not affect renal tubular handling of sodium. The enhanced tubular reabsorption of sodium post-frusemide, and the failure of ANF to suppress this, could be due to activation of the RAAS and SNS.

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The Role of Neuroendocrine Abnormalities in the Enhanced Sodium and Water Retention of Chronic Heart Failure

Abstract: Abbreviations:ACE -angiotensin converting enzyme; ACE1 -angiotensin converting enzyme inhibitor; A

Cited by 6 publications

References 58 publications

Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances

Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances

Diuretics

Frusemide pretreatment blunts the inhibition of renal tubular sodium reabsorption by ANF in man

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