Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats
Journal
Bratisl Lek Listy
Date Issued
2005
Author(s)
Abstract
Background: The synergistic effects of the combined ACE and NEP inhibition is based both on the
blockade of angiotensin II synthesis and degradation of vasoactive peptides and NEP substrates
(ANP, arginine, endothelial cells, guanylat cyclase etc.), including bradykinine and the
natriuretic peptides, which contribute to vasodilatation, diuresis and improvement of myocardial
function.
Objectives: This study was undertaken to asses the hypotensive effect of a dual ACE/NEP inhibitor
(omapatrilat) in comparison to a NEP inhibitor (candoxatril) and ACE inhibitor (enalapril) in SHRS.
Methods: The study was performed in 130 male spontaneously hypertensive rats (SHRS) that were
divided into 4 groups and treated orally by a gastric tube for 14 days according to the following
dosage regimen: omapatrilat (40 mg/kg b.w./24 h); candoxatril (30 mg/kg b.w./24 h); enalapril (20
mg/kg b.w./ 24 h) and control (water). Systolic blood pressure values were determined at the
beginning of the study by the tail-cuff pletysmographic method, at the 7th and 14th day of the
treatment, as well as 14 days after the end of the drug administration. For evaluation of the
effect of omapatrilat, candoxatril and enalapril on the investigated parameters (plasma atrial
natriuretic peptide and serum ACE), 10 ani- mals from the control group were sacrificed at the
beginning of the study, and afterwards 10 animals from each group were also sacrificed on the 7th
and 14th day of the treatment, as well as 14 days after the end of the drug administration (28th
day).
Results: The dual ACE/NEP inhibitor, omapatrilat and the ACE inhibitor, enalapril lowered SBP more
effectively than the NEP inhibitor, candoxatril at all time points of the experiment (p<0.01).
Omapatrilat was slightly more effective than the enalapril treatment.
Conclusions: Two-week treatment with the dual ACE/NEP inhibitor omapatrilat caused a significant
decrease of the SBP, inhibition of the serum ACE activity and increase of the plasma ANP values,
and therefore it should be considered as a new potential therapeutic agent in blood pressure
management.
blockade of angiotensin II synthesis and degradation of vasoactive peptides and NEP substrates
(ANP, arginine, endothelial cells, guanylat cyclase etc.), including bradykinine and the
natriuretic peptides, which contribute to vasodilatation, diuresis and improvement of myocardial
function.
Objectives: This study was undertaken to asses the hypotensive effect of a dual ACE/NEP inhibitor
(omapatrilat) in comparison to a NEP inhibitor (candoxatril) and ACE inhibitor (enalapril) in SHRS.
Methods: The study was performed in 130 male spontaneously hypertensive rats (SHRS) that were
divided into 4 groups and treated orally by a gastric tube for 14 days according to the following
dosage regimen: omapatrilat (40 mg/kg b.w./24 h); candoxatril (30 mg/kg b.w./24 h); enalapril (20
mg/kg b.w./ 24 h) and control (water). Systolic blood pressure values were determined at the
beginning of the study by the tail-cuff pletysmographic method, at the 7th and 14th day of the
treatment, as well as 14 days after the end of the drug administration. For evaluation of the
effect of omapatrilat, candoxatril and enalapril on the investigated parameters (plasma atrial
natriuretic peptide and serum ACE), 10 ani- mals from the control group were sacrificed at the
beginning of the study, and afterwards 10 animals from each group were also sacrificed on the 7th
and 14th day of the treatment, as well as 14 days after the end of the drug administration (28th
day).
Results: The dual ACE/NEP inhibitor, omapatrilat and the ACE inhibitor, enalapril lowered SBP more
effectively than the NEP inhibitor, candoxatril at all time points of the experiment (p<0.01).
Omapatrilat was slightly more effective than the enalapril treatment.
Conclusions: Two-week treatment with the dual ACE/NEP inhibitor omapatrilat caused a significant
decrease of the SBP, inhibition of the serum ACE activity and increase of the plasma ANP values,
and therefore it should be considered as a new potential therapeutic agent in blood pressure
management.
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