PPARalpha stimulation exerts a blood pressure lowering effect through different mechanisms in a time-dependent manner.
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 PPARalpha-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 (100mg/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 PPARalpha 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 AT(1)-receptor expression as well as angiotensin II decreased in clofibrate-treated rats, while angiotensin II AT(2)-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 PPARalpha 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.
Department of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico, D.F., Mexico City, Mexico.
Luz
L
Ibarra-Lara
Luz G
LG
Cervantes-Pérez
Francisca
F
Pérez-Severiano
Leonardo
L
Del Valle
Esther
E
Rubio-Ruíz
Elizabeth
E
Soria-Castro
Gustavo S
GS
Pastelín-Hernández
María
M
Sánchez-Aguilar
Juan C
JC
Martínez-Lazcano
Alicia
A
Sánchez-Mendoza
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001017:Aortic Coarctation / Q000150:complications; D001794:Blood Pressure / Q000187:drug effects; D002994:Clofibrate / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D047493:PPAR alpha; D017382:Reactive Oxygen Species; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D010088:Oxidoreductases; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; C028427:palmitoyl CoA oxidase; D002994:Clofibrate