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Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats

Chi Liu1, Chuan-Xi Yang1, Xi-Ru Chen1

  • 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

Amino Acids
|May 13, 2018
PubMed

Insights

Subcutaneous alamandine injection effectively reduces hypertension and cardiac hypertrophy in spontaneously hypertensive rats. This peptide improves left ventricle function and involves protein kinase A signaling pathways.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Molecular Biology

Background:

  • Hypertension frequently leads to cardiac damage, including left ventricle (LV) hypertrophy and impaired function.
  • The peptide alamandine has demonstrated antihypertensive and anti-fibrotic properties via oral administration in previous studies.
  • Investigating alternative administration routes like subcutaneous injection is crucial for therapeutic development.

Purpose of the Study:

  • To evaluate the efficacy of subcutaneous alamandine injection in attenuating hypertension and cardiac hypertrophy in spontaneously hypertensive rats (SHRs).
  • To assess the impact of alamandine on left ventricle (LV) function in SHRs.
  • To explore the underlying molecular mechanisms, including Mas-related G protein-coupled receptor, member D and protein kinase A (PKA) signaling.

Main Methods:

  • In vivo studies involved 6-week subcutaneous alamandine or saline infusion in SHRs and normotensive rats.
  • In vitro studies used H9C2 cells and primary neonatal rat cardiomyocytes treated with angiotensin II to model cardiac hypertrophy.
  • Measurements included tail artery blood pressure, transthoracic echocardiography, cardiac/lung mass, cardiomyocyte size, and gene/protein expression analysis.

Main Results:

  • Subcutaneous alamandine significantly ameliorated hypertension and impaired LV function in SHRs.
  • Alamandine administration reduced heart and lung mass, suppressed cardiomyocyte hypertrophy, and decreased atrial natriuretic peptide and brain natriuretic peptide mRNA levels.
  • Increased expression of the alamandine receptor (MrgD) and inhibition of PKA levels were observed in response to alamandine treatment.

Conclusions:

  • Subcutaneous alamandine administration is a viable strategy to attenuate hypertension, cardiac hypertrophy, and improve LV function in SHRs.
  • The therapeutic effects of alamandine appear to be mediated, at least in part, through the modulation of PKA signaling pathways.
  • Further research into alamandine's role in cardiovascular protection is warranted.
Keywords:
AlamandineCardiac hypertrophyHypertensionProtein kinase ASpontaneously hypertensive rats

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