Differential actions of vasopeptidase inhibition versus angiotensin-converting enzyme inhibition on diuretic therapy in experimental congestive heart failure

Alessandro Cataliotti, Guido Boerrigter, Horng Haur Chen, Michihisa Jougasaki, Lisa C. Costello, Toshihiro Tsuruda, Shang Chiun Lee, Lorenzo S. Malatino, John C Jr. Burnett

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background - Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial cardiorenal and humoral properties of the natriuretic peptides, we hypothesized that an acute vasopeptidase inhibitor with or without diuretic would result in more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic (ACEI+D) in congestive heart failure. Methods and Results - We compared the actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing-induced congestive heart failure. OMA+D decreased pulmonary arterial and pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D. Glomerular filtration rate was lower with ACEI+D than with either OMA group. Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas OMA+D resulted in higher plasma renin activity and a delayed increase in aldosterone. OMA alone did not increase plasma renin activity and aldosterone, but resulted in a sustained increase in plasma adrenomedullin, with higher urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with ACEI+D. Conclusions - Acute administration of OMA with or without diuretic results in more favorable cardiorenal and humoral responses in experimental congestive heart failure than does ACEI+D. There is no acute activation of renin and aldosterone with OMA alone such as occurs with ACE[+D and OMA+D. Thus, OMA with or without a diuretic possesses beneficial cardiorenal and humoral actions comparable to those observed with ACEI+D that can be explained by potentiation of natriuretic peptides.

Original languageEnglish (US)
Pages (from-to)639-644
Number of pages6
JournalCirculation
Volume105
Issue number5
DOIs
StatePublished - Feb 5 2002

Fingerprint

Investigational Therapies
Peptidyl-Dipeptidase A
Diuretics
Heart Failure
Aldosterone
Renin
Natriuretic Peptides
Adrenomedullin
omapatrilat
Neprilysin
Pulmonary Wedge Pressure
Atrial Natriuretic Factor
Glomerular Filtration Rate

Keywords

  • Heart failure
  • Natriuretic peptides
  • Omapatrilat

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Differential actions of vasopeptidase inhibition versus angiotensin-converting enzyme inhibition on diuretic therapy in experimental congestive heart failure. / Cataliotti, Alessandro; Boerrigter, Guido; Chen, Horng Haur; Jougasaki, Michihisa; Costello, Lisa C.; Tsuruda, Toshihiro; Lee, Shang Chiun; Malatino, Lorenzo S.; Burnett, John C Jr.

In: Circulation, Vol. 105, No. 5, 05.02.2002, p. 639-644.

Research output: Contribution to journalArticle

Cataliotti, Alessandro ; Boerrigter, Guido ; Chen, Horng Haur ; Jougasaki, Michihisa ; Costello, Lisa C. ; Tsuruda, Toshihiro ; Lee, Shang Chiun ; Malatino, Lorenzo S. ; Burnett, John C Jr. / Differential actions of vasopeptidase inhibition versus angiotensin-converting enzyme inhibition on diuretic therapy in experimental congestive heart failure. In: Circulation. 2002 ; Vol. 105, No. 5. pp. 639-644.
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abstract = "Background - Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial cardiorenal and humoral properties of the natriuretic peptides, we hypothesized that an acute vasopeptidase inhibitor with or without diuretic would result in more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic (ACEI+D) in congestive heart failure. Methods and Results - We compared the actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing-induced congestive heart failure. OMA+D decreased pulmonary arterial and pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D. Glomerular filtration rate was lower with ACEI+D than with either OMA group. Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas OMA+D resulted in higher plasma renin activity and a delayed increase in aldosterone. OMA alone did not increase plasma renin activity and aldosterone, but resulted in a sustained increase in plasma adrenomedullin, with higher urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with ACEI+D. Conclusions - Acute administration of OMA with or without diuretic results in more favorable cardiorenal and humoral responses in experimental congestive heart failure than does ACEI+D. There is no acute activation of renin and aldosterone with OMA alone such as occurs with ACE[+D and OMA+D. Thus, OMA with or without a diuretic possesses beneficial cardiorenal and humoral actions comparable to those observed with ACEI+D that can be explained by potentiation of natriuretic peptides.",
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T1 - Differential actions of vasopeptidase inhibition versus angiotensin-converting enzyme inhibition on diuretic therapy in experimental congestive heart failure

AU - Cataliotti, Alessandro

AU - Boerrigter, Guido

AU - Chen, Horng Haur

AU - Jougasaki, Michihisa

AU - Costello, Lisa C.

AU - Tsuruda, Toshihiro

AU - Lee, Shang Chiun

AU - Malatino, Lorenzo S.

AU - Burnett, John C Jr.

PY - 2002/2/5

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N2 - Background - Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial cardiorenal and humoral properties of the natriuretic peptides, we hypothesized that an acute vasopeptidase inhibitor with or without diuretic would result in more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic (ACEI+D) in congestive heart failure. Methods and Results - We compared the actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing-induced congestive heart failure. OMA+D decreased pulmonary arterial and pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D. Glomerular filtration rate was lower with ACEI+D than with either OMA group. Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas OMA+D resulted in higher plasma renin activity and a delayed increase in aldosterone. OMA alone did not increase plasma renin activity and aldosterone, but resulted in a sustained increase in plasma adrenomedullin, with higher urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with ACEI+D. Conclusions - Acute administration of OMA with or without diuretic results in more favorable cardiorenal and humoral responses in experimental congestive heart failure than does ACEI+D. There is no acute activation of renin and aldosterone with OMA alone such as occurs with ACE[+D and OMA+D. Thus, OMA with or without a diuretic possesses beneficial cardiorenal and humoral actions comparable to those observed with ACEI+D that can be explained by potentiation of natriuretic peptides.

AB - Background - Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial cardiorenal and humoral properties of the natriuretic peptides, we hypothesized that an acute vasopeptidase inhibitor with or without diuretic would result in more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic (ACEI+D) in congestive heart failure. Methods and Results - We compared the actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing-induced congestive heart failure. OMA+D decreased pulmonary arterial and pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D. Glomerular filtration rate was lower with ACEI+D than with either OMA group. Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas OMA+D resulted in higher plasma renin activity and a delayed increase in aldosterone. OMA alone did not increase plasma renin activity and aldosterone, but resulted in a sustained increase in plasma adrenomedullin, with higher urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with ACEI+D. Conclusions - Acute administration of OMA with or without diuretic results in more favorable cardiorenal and humoral responses in experimental congestive heart failure than does ACEI+D. There is no acute activation of renin and aldosterone with OMA alone such as occurs with ACE[+D and OMA+D. Thus, OMA with or without a diuretic possesses beneficial cardiorenal and humoral actions comparable to those observed with ACEI+D that can be explained by potentiation of natriuretic peptides.

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