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January 1, 2000Hypertension

Release of Angiotensin-(1-7) From the Rat Hindlimb

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Population

Rat hindlimb perfused with Krebs-Ringer buffer containing Ficoll

Comparison

ACE inhibitor lisinopril or neprilysin inhibitor… vs Control buffer

Design

Preclinical

Authors

MCMark C. ChappellHeart Failure & TransplantMGMartina N. GomezWake Forest UniversityNPNancy T. PirroWake Forest University

Discussion

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Implication

Should not alter current antihypertensive prescribing; leaves open whether this neprilysin-dependent mechanism contributes.

Key Points

  • This study investigates the effects of ACE inhibition on the release of angiotensin-(1-7) from rat hindlimb tissues.
  • Rat hindlimb perfusion with Krebs-Ringer buffer containing Ficoll
  • Addition of ACE inhibitor lisinopril to evaluate angiotensin-(1-7) release
  • Use of HPLC and radioimmunoassay to analyze effluent components.
  • Inhibition of ACE significantly increased angiotensin-(1-7) levels to 144+/-39 fmol and 163+/-35 fmol (P<0.05) during treatment periods.
  • Neprilysin inhibition reduced angiotensin-(1-7) to 112+/-24 fmol and 87+/-23 fmol (P<0.05), showing its role in peptide metabolism.
  • No formation of Ang II was detected during angiotensin I metabolism in the collected perfusate.

Structured PICO

P
Population
Rat hindlimb perfused with Krebs-Ringer buffer containing Ficoll (n=8 for lisinopril experiment, n=6 for SCH 39370 experiment)
I
Intervention
ACE inhibitor lisinopril or neprilysin inhibitor SCH 39370 added to perfusion buffer
C
Comparator
Control buffer (baseline periods prior to intervention)
O
Outcome
Angiotensin-(1-7) release levelssurrogate

ACE inhibition significantly increases the release of endogenous Ang-(1-7) from the rat hindlimb, partially dependent on neprilysin activity.

Cite This Study

Chappell et al. (2000) studied this question.

synapsesocial.com/papers/6a227e77ffccceb004b72eechttps://doi.org/10.1161/01.hyp.35.1.348
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Angiotensin-(1-7). A member of circulating angiotensin peptides.1991 · 108 citations
  2. 2Modulation of Ca2+-gated cardiac muscle Ca2+-release channel (ryanodine receptor) by mono- and divalent ions1998 · 91 citations
  3. 3Converting Enzyme Determines Plasma Clearance of Angiotensin-(1–7)1998 · 204 citations
  4. 4Metabolism of Angiotensin-(1–7) by Angiotensin-Converting Enzyme1998 · 291 citations
  5. 5Antihypertensive effects of angiotensin-(1-7)1998 · 55 citations