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May 6, 2015AJP Regulatory Integrative and Comparative Physiology

Angiotensin receptors alter myocardial infarction-induced remodeling of the guinea pig cardiac plexus

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Key result

In guinea pigs with chronic myocardial infarction, treatment with the AT2 receptor agonist CGP42112A prevented the disease-induced increase in neuronal sensitivity to norepinephrine, while the AT1 antagonist losartan enhanced synaptic efficacy.

Population

9-week-old male Hartley guinea pigs weighing 500-650 g with surgically induced chronic myocardial infarction…

Comparison

Chronic treatment with captopril, losartan, or… vs Untreated MI animals and healthy control animals.

Design

Preclinical

Follow-up

6 to 7 weeks

Authors

JHJean C. HardwickIthaca CollegeSRShannon RyanAstraZeneca (India)EPEmily Nicole Powers

Discussion

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Implication

Should not change post-MI care; leaves open whether AT1/AT2 modulation alters human cardiac neuronal remodeling.

Structured PICO

P
Population
70 nine-week-old male Hartley guinea pigs subjected to surgically induced myocardial infarction or sham surgery, followed for 6 to 7 weeks.
I
Intervention
Chronic treatment (6 weeks via subcutaneous osmotic pump) with captopril (3 mg/kg/day), losartan (3 mg/kg/day), or CGP42112A (0.14 mg/kg/day).
C
Comparator
Untreated MI animals and healthy control animals (with or without drug treatment).
O
Outcome
Neuronal excitability and responses to norepinephrine (NE), bethanechol, or ANG II, and AT1/AT2 receptor expression in the intrinsic cardiac plexus.surrogate

Main Result

p-value: p=<0.05

In a guinea pig model of MI, neuronal remodeling of the cardiac plexus is mediated by both AT1 and AT2 receptors, and can be modulated by angiotensin receptor-targeted therapies.

Limitations

  • Animal model may not fully translate to human chronic heart disease
  • High variability in protein band densities for captopril treatment made it difficult to draw definitive conclusions

Cite This Study

Hardwick et al. (2015) studied Myocardial infarction (n=70). Angiotensin receptor modulators (captopril, losartan, CGP42112A) vs. Untreated MI or sham controls was evaluated on Neuronal excitability to norepinephrine and angiotensin II (p=<0.05). In guinea pigs with chronic myocardial infarction, treatment with the AT2 receptor agonist CGP42112A prevented the disease-induced increase in neuronal sensitivity to norepinephrine, while the AT1 antagonist losartan enhanced synaptic efficacy.

synapsesocial.com/papers/6a9b02feeca8f8ecbc8abe8dhttps://doi.org/10.1152/ajpregu.00004.2015
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Also Consider

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

  1. 1Angiotensin II potentiates adrenergic and muscarinic modulation of guinea pig intracardiac neurons2011 · 11 citations
  2. 2ANG II modifies cardiomyocyte function via extracardiac and intracardiac neurons: in situ and in vitro studies1997 · 28 citations
  3. 3Angiotensin AT1–Receptor Blockers Enhance Cardiac Responses to Parasympathetic Nerve Stimulation via Presynaptic AT1 Receptors in Pithed Rats2013 · 10 citations
  4. 4Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT<sub>1</sub> receptors in heart failure2008 · 82 citations
  5. 5Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function2013 · 130 citations