Inhibition of brain renin-angiotensin system improves diastolic cardiac function following myocardial infarction in rats.

1. Recently, we demonstrated that oral captopril treatment improved diastolic function and attenuated cardiac remodelling after myocardial infarction (MI) in rats. Considering the feasible role of the brain renin-angiotensin system (RAS) in heart failure, in the present study we investigated the role of the captopril injected intracerebroventricularly (i.c.v.) on the progression of cardiac dysfunction. 2. Male Wistar rats underwent experimental MI or sham operation. Infarcted animals received daily i.c.v. injections of captopril (approximately 200 mg/kg; MI + Cap) or saline (MI) from 11 to 18 days after infarction. Electro- and echocardiogram assessments were performed before and after i.c.v. treatment (10 and 18 days after MI, respectively). Water and hypertonic saline ingestion were determined daily between 12 and 16 days after MI. 3. Electrocardiograms from the MI and MI + Cap groups showed signs that resembled large MI before and after i.c.v. treatment. However, despite similar systolic dysfunction observed in both groups, only captopril-treated rats exhibited reduced left ventricular (LV) dilatation and improved LV filling, as assessed by echocardiograms, and low levels of water ingestion compared with the saline-treated control group. 4. The results of the present study suggest that the brain RAS may participate in the development of cardiac dysfunction induced by ischaemia and that inhibition of the brain RAS may provide a new strategy for the prevention of diastolic dysfunction.
AuthorsI G Araujo, D C Trindade, A S Mecawi, Rafael Sonoda-Côrtes, J P S Werneck-de-Castro, R H Costa-E-Sousa, L C Reis, E L Olivares
JournalClinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 36 Issue 8 Pg. 803-9 (Aug 2009) ISSN: 1440-1681 [Electronic] Australia
PMID19215232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Captopril
  • Angiotensin-Converting Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
  • Animals
  • Brain (drug effects, metabolism)
  • Captopril (administration & dosage, pharmacology, therapeutic use)
  • Diastole (drug effects)
  • Disease Models, Animal
  • Echocardiography
  • Electrocardiography
  • Injections, Intraventricular
  • Male
  • Myocardial Infarction (metabolism, physiopathology, ultrasonography)
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System (drug effects)

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