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March 9, 2004Hypertension

Upregulation of Angiotensin-Converting Enzyme 2 After Myocardial Infarction by Blockade of Angiotensin II Receptors

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Key result

Angiotensin II receptor blockade with losartan or olmesartan completely reversed the reduction in cardiac AT1a-R mRNA after myocardial infarction and augmented ACE 2 mRNA by approximately 3-fold.

Why the study?

Does angiotensin II receptor blockade upregulate cardiac ACE2 expression in rats after myocardial infarction?

Population

Lewis normotensive rats subjected to coronary artery ligation (myocardial infarction) or sham operation

Comparison

Losartan or olmesartan administered via osmotic… vs Vehicle administered via osmotic minipumps

Design

Preclinical

Follow-up

28 days

Authors

YIYuichiro IshiyamaJoled (Japan)PGPatricia E. GallagherWake Forest UniversityDADavid B. AverillGeisinger Commonwealth School of Medicine

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Implication

Hypothesis-generating for ARB effects on cardiac ACE2 post-MI in rats; leaves open human translation.

Key Points

  • This research aims to explore how blocking angiotensin II receptors affects cardiac enzyme expression after a heart attack.
  • Conducted in Lewis normotensive rats following coronary artery ligation or sham operation.
  • Administered losartan, olmesartan, or vehicle via osmotic minipumps for 28 days post-surgery.
  • Measured plasma angiotensins and cardiac mRNA expression for ACE, ACE 2, and AT1a-R.
  • Both losartan and olmesartan completely reversed the reduction in cardiac AT1a-R mRNA post-ligation.
  • Losartan and olmesartan increased ACE 2 mRNA expression by approximately 3-fold.
  • Olmesartan improved ventricular contractility and both drugs attenuated cardiac hypertrophy.

Structured PICO

Does angiotensin II receptor blockade upregulate cardiac ACE2 expression in rats after myocardial infarction?

P
Population
Lewis normotensive rats subjected to coronary artery ligation (myocardial infarction) or sham operation
I
Intervention
Losartan or olmesartan administered via osmotic minipumps for 28 days
C
Comparator
Vehicle (isotonic saline) administered via osmotic minipumps
O
Outcome
Expression of cardiac angiotensin-converting enzymes (ACE and ACE 2) and angiotensin II type-1 receptors (AT1a-R) mRNAsurrogate

Angiotensin II receptor blockade with losartan or olmesartan upregulates cardiac ACE2 mRNA expression in rats after myocardial infarction, suggesting a potential mechanism for their cardioprotective effects.

Cite This Study

Ishiyama et al. (2004) studied Myocardial infarction. Losartan or olmesartan vs. Vehicle (isotonic saline) was evaluated on Expression of cardiac angiotensin-converting enzymes (ACE and ACE 2) and angiotensin II type-1 receptors (AT1a-R). Angiotensin II receptor blockade with losartan or olmesartan completely reversed the reduction in cardiac AT1a-R mRNA after myocardial infarction and augmented ACE 2 mRNA by approximately 3-fold.

synapsesocial.com/papers/6a1c7b0d0e2acd31eb2fcccbhttps://doi.org/10.1161/01.hyp.0000124667.34652.1a

Topics

Hypertrophic cardiomyopathy
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Also Consider

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

  1. 1Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat.1994 · 422 citations
  2. 2Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.1995 · 439 citations
  3. 3Angiotensin-(1–7) Attenuates the Development of Heart Failure After Myocardial Infarction in Rats2002 · 322 citations
  4. 4Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.1997 · 606 citations
  5. 5Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression1998 · 242 citations