PPARα Stimulation Modulates Myocardial Ischemia-induced Activation of Renin-Angiotensin System.

Abstract

We have recently demonstrated that peroxisome proliferator-activated receptor alpha (PPARα) stimulation lowers the production of angiotensin II while increasing the production of Ang-(1-7), both in cardiac and plasmatic level. This stimulation improves nitric oxide bioavailability, preserving cardiac histologic features and functioning. Based on these results, we decided to study the effect of PPARα stimulation on renin-angiotensin system components of ischemic myocardium. Male Wistar rats (weighing 300-350 g) were assigned to the following groups: (1) sham, (2) myocardial ischemia vehicle-treated (MI-V), and (3) myocardial ischemia clofibrate-treated. Expression of the angiotensin-converting enzyme increased during ischemia, whereas clofibrate-treated group remained comparable to control. Activation of the PPARα receptor stimulated the expression of angiotensin-converting enzyme-2; while the activity of this enzyme was increased in MI-V, clofibrate inhibited any change. The concentration of bradykinin and phospho-Akt(SER473) in homogenate increased in the animals treated with the drug. Mas receptor expression increased in MI-V rats. In conclusion, stimulation of PPARα by clofibrate prevents an increase in the activity of renin-angiotensin system and promotes the production of vasodilator substances.

• Authors: Luz Ibarra-Lara, María Sánchez-Aguilar, Enrique Hong, Leonardo del Valle-Mondragón, Elizabeth Soria-Castro, Francisca Pérez-Severiano, Juan Carlos Torres-Narváez, Margarita Ramírez-Ortega, Gustavo S Pastelín-Hernández, Luz G Cervantes-Pérez, Alicia Sánchez-Mendoza
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 65 Issue 5 Pg. 430-7 (May 2015) ISSN: 1533-4023 [Electronic] United States
• PMID: 25658458 (Publication Type: Journal Article)

Chemical References

• PPAR alpha
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Receptors, G-Protein-Coupled
• Serine
• Proto-Oncogene Proteins c-akt
• Peptidyl-Dipeptidase A
• Ace2 protein, rat
• Angiotensin-Converting Enzyme 2
• Clofibrate
• Bradykinin

Topics

• Angiotensin-Converting Enzyme 2
• Animals
• Bradykinin (metabolism)
• Clofibrate (pharmacology)
• Disease Models, Animal
• Enzyme Activation
• Male
• Myocardial Ischemia (drug therapy, metabolism, physiopathology)
• Myocardium (metabolism)
• PPAR alpha (agonists, metabolism)
• Peptidyl-Dipeptidase A (metabolism)
• Phosphorylation
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Wistar
• Receptors, G-Protein-Coupled (metabolism)
• Renin-Angiotensin System (drug effects)
• Serine
• Signal Transduction (drug effects)
• Vasodilation (drug effects)