Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9279
Title: Beneficial renal and cardiac effects of vasopeptidase inhibition with S21402 in heart failure.
Authors: Burrell, Louise M;Farina, N K;Balding, Leanne C;Johnston, Colin I
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Victoria, Australia. burrell@austin.unimelb.edu.au
Issue Date: 1-Dec-2000
Citation: Hypertension; 36(6): 1105-11
Abstract: S21402 is a vasopeptidase inhibitor that simultaneously inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). This study determined whether chronic treatment with S21402 produced different effects on sodium and water excretion, hormonal parameters, and cardiovascular structure compared with selective inhibition of ACE and NEP in a rat model of myocardial infarction-induced congestive heart failure (CHF). CHF rats received the vasopeptidase inhibitor (S21402, 100 mg. kg(-1). d(-1)), an ACE inhibitor (captopril, 50 mg. kg(-1). d(-1)), a NEP inhibitor (SCH42495, 60 mg. kg(-1). d(-1)), or vehicle for 4 weeks. S21402 alone caused a diuresis and natriuresis (P<0.01) in CHF. After 4 weeks, blood pressure was lowered by captopril but not other treatments (P<0.01). Both S21402 and captopril increased plasma renin activity (P<0.01), all treatment lowered plasma aldosterone (P<0.05) and plasma natriuretic peptide levels were unchanged. In the kidney, S21402 inhibited NEP and ACE (P<0.01), SCH42495 inhibited NEP (P<0.01), and captopril inhibited ACE (P<0.01). Heart mass was reduced by all active treatments; captopril reduced left ventricular mass (P<0.01), SCH42495 reduced right ventricular mass (P<0.01), and S21402 decreased left (P<0.05) and right ventricular mass (P<0.01), atrial mass (P<0.05), and lung mass (P<0.01). In CHF, vasopeptidase inhibition with S21402 produces effects that differ from those of selective NEP or ACE inhibition. S21402 improved sodium and water excretion, reduced pulmonary congestion, and attenuated both right and left ventricular remodeling. These effects, which occurred in the absence of any hypotensive action, suggest that S21402 may offer several advantages over ACE inhibition alone in the treatment of heart failure.
Internal ID Number: 11116133
URI: http://ahro.austin.org.au/austinjspui/handle/1/9279
URL: http://www.ncbi.nlm.nih.gov/pubmed/11116133
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Animals
Blood Pressure.drug effects
Body Weight.drug effects
Captopril.therapeutic use
Cardiovascular System.drug effects.physiopathology
Disease Models, Animal
Female
Heart Failure.drug therapy.metabolism.physiopathology
Hormones.metabolism
Kidney.drug effects
Methionine.analogs & derivatives.therapeutic use
Myocardial Infarction.etiology
Neprilysin.antagonists & inhibitors
Propionates.therapeutic use
Protease Inhibitors.therapeutic use
Rats
Rats, Sprague-Dawley
Sulfhydryl Compounds.therapeutic use
Water.metabolism
Appears in Collections:Journal articles

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