PPARalpha activator effects on Ang II-induced vascular oxidative stress and inflammation.
Docosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-alpha (PPARalpha) activator, reduces blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that DHA would prevent BP elevation and improve vascular dysfunction in angiotensin (Ang) II-infused rats by modulating of NADPH oxidase activity and inflammation in vascular wall. Sprague-Dawley rats received Ang II (120 ng/kg per minute SC) with or without DHA (2.5 mL of oil containing 40% DHA/d PO) for 7 days. Systolic BP (mm Hg), elevated in Ang II-infused rats (172+/-3) versus controls (108+/-2, P<0.01), was reduced by DHA (112+/-4). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (P<0.05) and acetylcholine-induced relaxation impaired in Ang II-infused rats (P<0.05); both were normalized by DHA. In blood vessels of Ang II-infused rats, NADPH oxidase activity measured by chemiluminescence and expression of adhesion molecules intercellular adhesion molecule and vascular cell adhesion molecule-1 were significantly increased. These changes were abrogated by DHA. PPARalpha activator DHA attenuated the development of hypertension, corrected structural abnormalities, and improved endothelial dysfunction induced by Ang II. These effects are associated with decreased oxidative stress and inflammation in the vascular wall.
Diep
Quy N
QN
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Amiri
Farhad
F
Touyz
Rhian M
RM
Cohn
Jeffrey S
JS
Endemann
Dierk
D
Neves
Mario Fritsch
MF
Schiffrin
Ernesto L
EL
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006973:Hypertension / Q000517:prevention & control; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D012083:Renin / Q000097:blood; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D014665:Vasodilator Agents / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D005230:Fatty Acids, Nonesterified; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D000804:Angiotensin II; D004281:Docosahexaenoic Acids; D000450:Aldosterone; D002784:Cholesterol; D019255:NADPH Oxidases; D012083:Renin