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PPARα stimulation exerts a blood pressure lowering effect through different mechanisms in a time-dependent manner

2009; Elsevier BV; Volume: 627; Issue: 1-3 Linguagem: Inglês

10.1016/j.ejphar.2009.10.039

1879-0712

Luz Ibarra-Lara, Luz Graciela Cervantes-Pérez, Francisca Pérez‐Severiano, Leonardo del Valle‐Mondragón, María Esther Rubio-Ruíz, Elizabeth Soria‐Castro, Gustavo Pastelín-Hernández, María Sánchez-Aguilar, Juan Carlos Martínez‐Lazcano, Alicia Sánchez-Mendoza,

Eicosanoids and Hypertension Pharmacology

Peroxisome proliferator activated receptors (PPARs) are a family of nuclear receptors that, upon activation with selective ligands, work as transcription factors. Recently, these have been related with the cardiovascular system. Our aim was to study PPARα-stimulation and its effects on blood pressure in rats with aortic coarctation, and to explore the role of the antioxidant system. Male Wistar rats (250–280 g) were distributed into the following groups: 1) sham; 2) aortic coarctated-vehicle-treated (AoCo-V), and 3) AoCo-clofibrate (100 mg/kg) treated (AoCo-C). Rats were treated for 1 or 21 days. Clofibrate lowered blood pressure in both 1- and 21-day treatments. Renal reactive oxygen species increased after 1 day in AoCo-V, while clofibrate prevented this effect. Superoxide dismutase (SOD)-1 expression increased 3.6-fold upon PPARα stimulation (1 day) and returned to normal values by day 21. SOD-1 activity increased slightly in response to clofibrate. Renal activity of catalase increased in AoCo-C (1 day) and returned to normal (21 days). eNOS expression was not modified acutely (1 day) but increased at 21 days of treatment with clofibrate. Angiotensin II AT1-receptor expression as well as angiotensin II decreased in clofibrate-treated rats, while angiotensin II AT2-receptor expression increased, in both treatment periods. Angiotensin-(1–7) increased at 21 days. Our results suggest that in the early development of AoCo-induced hypertension, stimulation of PPARα increases the antioxidant defenses, leading to improvement in endothelial factors while in the sub-chronic phase (21 days), eNOS and angiotensin II receptors appear to play major roles in controlling blood pressure.