Wine polyphenols improve endothelial function in large vessels of female spontaneously hypertensive rats.
Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction. Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F(2alpha) excretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitor l-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) expression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F(2alpha) excretion, and aortic O(2)(-) production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) expression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function.
López-Sepúlveda
Rocío
R
Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain.
Jiménez
Rosario
R
Romero
Miguel
M
Zarzuelo
Maria José
MJ
Sánchez
Manuel
M
Gómez-Guzmán
Manuel
M
Vargas
Félix
F
O'Valle
Francisco
F
Zarzuelo
Antonio
A
Pérez-Vizcaíno
Francisco
F
Duarte
Juan
J
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D028421:Isoprostanes / Q000652:urine; D007668:Kidney / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D014920:Wine
C495537:Cav1 protein, rat; D051242:Caveolin 1; D005419:Flavonoids; D028421:Isoprostanes; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1