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.
Ibarra-Lara
Luz
L
Department of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico, D.F., Mexico City, Mexico.
Cervantes-Pérez
Luz G
LG
Pérez-Severiano
Francisca
F
Del Valle
Leonardo
L
Rubio-Ruíz
Esther
E
Soria-Castro
Elizabeth
E
Pastelín-Hernández
Gustavo S
GS
Sánchez-Aguilar
María
M
Martínez-Lazcano
Juan C
JC
Sánchez-Mendoza
Alicia
A
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