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Angiotensin-converting enzyme inhibition and angiotensin II subtype-1 receptor blockade during the progression of

F G Spinale1, H H Holzgrefe, R Mukherjee

  • 1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.

The Journal of Pharmacology and Experimental Therapeutics
|February 12, 1998
PubMed

Insights

Angiotensin-converting enzyme (ACE) inhibition improves heart function in chronic left ventricular (LV) dysfunction, but not via the AT1 receptor. ACE inhibition benefits LV and myocyte function, unlike AT1 receptor blockade.

Area of Science:

  • Cardiology
  • Pharmacology
  • Physiology

Background:

  • Chronic left ventricular (LV) dysfunction is often treated with angiotensin-converting enzyme (ACE) inhibitors, improving survival and symptoms.
  • The direct impact of ACE inhibition on myocyte contractility and the role of the AT1 angiotensin-II receptor subtype remain incompletely understood.

Purpose of the Study:

  • To investigate the direct effects of ACE inhibition on LV and myocyte function.
  • To determine if these effects are mediated through the AT1 angiotensin-II receptor subtype.

Main Methods:

  • Four groups of dogs were studied: chronic rapid pacing (LV failure), rapid pacing with ACE inhibition (fosinopril), rapid pacing with AT1 receptor blockade (irbesartan), and controls.
  • Left ventricular (LV) geometry, ejection fraction, myocyte contractile function, beta-adrenergic receptor density, and cyclic AMP production were assessed.

Main Results:

  • Chronic rapid pacing significantly worsened LV and myocyte function.
  • ACE inhibition improved LV geometry, ejection fraction, and myocyte contractility, while normalizing beta-receptor density and cyclic AMP production.
  • AT1 receptor blockade failed to improve LV or myocyte function, despite normalizing beta-receptor density.

Conclusions:

  • ACE inhibition confers beneficial effects on LV and myocyte function in the setting of developing LV failure.
  • These protective effects are not primarily mediated through the AT1 angiotensin-II receptor.
  • The findings suggest a distinct mechanism for ACE inhibition's benefits beyond AT1 receptor blockade.

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