Polyphenols restore endothelial function in DOCA-salt hypertension: Role of endothelin-1 and NADPH oxidase

Jiménez, Rosario; López-Sepúlveda, R; Kadmiri, María; Romero, Miguel; Vera, Rocío; Sánchez, Manuel; Vargas, Félix; O’Valle, Francisco; Zarzuelo, Antonio; Dueñas, Montserrat

doi:10.1016/j.freeradbiomed.2007.05.007

Cited by 92 publications

(61 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The descending thoracic aortic rings were dissected and mounted in organ chambers filled with Krebs' solution (118 mM NaCl, 4.75 mM KCl, 25 mM NaHCO 3 , 1.2 mM MgSO 4 , 2 mM CaCl 2 , 1.2 mM KH 2 PO 4 , and 11 mM glucose) at 37°C and gassed with 95% O 2 and 5% CO 2 . Rings were stretched to 2 g of resting tension by means of two L-shaped stainless steel wires inserted into the lumen and attached to the chamber and an isometric forcedisplacement transducer (Letigraph 2000; Letica S.A., Barcelona, Spain), respectively, as described previously (Jiménez et al, 2007), and equilibrated for 60 to 90 min. In some arteries, the endothelium was mechanically removed by gently rubbing the intimal surface of the rings with a metal rod.…”

Section: Methodsmentioning

confidence: 99%

Endothelium-Dependent Vasodilator Effects of Peroxisome Proliferator-Activated Receptor β Agonists via the Phosphatidyl-Inositol-3 Kinase-Akt Pathway

Jiménez

Sánchez²,

Zarzuelo³

et al. 2009

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor ␤/␦ (PPAR-␤) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily that regulates the transcription of many target genes. More recently, acute, nongenomic effects of PPAR-␤ agonists have also been described. In the present study, we hypothesized that PPAR-␤ agonists might exert acute nongenomic effects on vascular tone. Here, we report that the structurally unrelated PPAR-␤ ligands [4-[3-(4-acetyl- sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660) also partially inhibited these relaxant responses, although PPAR-␥ blockade with 2-chloro-5-nitro-N-phenylbenzamide (GW9662) had no effect. In human umbilical vein endothelial cells, L-165041 and GW0742 increased nitric oxide (NO) production and Akt and endothelial NOS (eNOS) phosphorylation, which were sensitive to PI3K inhibition and PPAR-␤ blockade. In conclusion, the PPAR-␤ agonists acutely caused vasodilatation, which was partially dependent on endothelial-derived NO. The eNOS activation is calciumindependent and seems to be related to activation of the PI3K-Akt-eNOS pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

Endothelium-Dependent Vasodilator Effects of Peroxisome Proliferator-Activated Receptor β Agonists via the Phosphatidyl-Inositol-3 Kinase-Akt Pathway

Jiménez

Sánchez²,

Zarzuelo³

et al. 2009

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rings were stretched to 2 g of resting tension by means of 2 L-shaped stainless-steel wires inserted into the lumen and attached to the chamber and to an isometric force-displacement transducer (Letigraph 2000), respectively, as previously described. 32 The concentration-relaxation response curves to acetylcholine (ACh) (10 Ϫ9 mol/L to 10 Ϫ4 mol/L) were performed in rings pre-contracted by 10 Ϫ6 mol/L phenylephrine. The concentration-relaxation response curves to nitroprusside (10 Ϫ9 mol/L to 10 Ϫ5 mol/L) were performed in the dark in rings pre-contracted by 10 Ϫ6 mol/L phenylephrine.…”

Section: Vascular Reactivity Studiesmentioning

confidence: 99%

Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

et al. 2008

Self Cite

View full text Add to dashboard Cite

Abstract-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 2␣ 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 2␣ excretion, and aortic O 2 Ϫ 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. Key Words: red wine polyphenols Ⅲ spontaneously hypertensive rat Ⅲ endothelial dysfunction Ⅲ NADPH oxidase Ⅲ ovariectomy T he incidence of cardiovascular diseases among premenopausal women is lower than age-matched, men but it rises markedly after menopause. Blood pressure is also higher in men than in women at similar ages, 1 and this difference is also reduced or even inverted after menopause. The loss of estrogens has been suggested as a major risk factor for postmenopausal hypertension. Estrogen receptor (ER) subtypes ER␣ and ER␤ are expressed in endothelial and smooth muscle cells. [2][3][4][5] Estrogens increase endothelial-derived NO, modulate the local tissue reninangiotensin system, and show antioxidant effects. [3][4][5][6][7][8][9][10] Long-term estrogen treatment improves endothelial dysfunction, through upregulation of endothelial nitric oxide synthase (eNOS), 11,12 posttranslational modulation of eNOS activity, 13 or nongenomic effects, including activation of NO synthesis. 14,15 However, despite the positive effects on vascular function found in cell culture, 12,14 ex vivo 15 and in vivo animal 16 -18 and short-term human 7,19 -21 studies, estrogen replacement therapy has failed to protect from cardiovascular diseases in large scale randomized controlled ...

show abstract

“…It has also been shown to be induced by oxidants with such induction also lowered by antioxidants [202][203][204]. e activity of ET-1 has been shown to be increased by both NF-B action and also the action of another in�ammatory cytokine activated pathway [205][206][207].…”

Section: Principlementioning

confidence: 99%

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Pall

2013

ISRN Hypertension

View full text Add to dashboard Cite

e NO/ONOO − cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic in�ammatory diseases. is paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. e cycle involves 12 elements, including superoxide, peroxynitrite (ONOO − ), nitric oxide (NO), oxidative stress, NF-B, in�ammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. is extraordinary �t to the principles of the NO/ONOO − cycle allows one to conclude that PAH is a NO/ONOO − cycle disease, and this �t supports the cycle as a ma�or paradigm of chronic in�ammatory disease.

show abstract

Polyphenols restore endothelial function in DOCA-salt hypertension: Role of endothelin-1 and NADPH oxidase

Cited by 92 publications

References 58 publications

Endothelium-Dependent Vasodilator Effects of Peroxisome Proliferator-Activated Receptor β Agonists via the Phosphatidyl-Inositol-3 Kinase-Akt Pathway

Endothelium-Dependent Vasodilator Effects of Peroxisome Proliferator-Activated Receptor β Agonists via the Phosphatidyl-Inositol-3 Kinase-Akt Pathway

Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Contact Info

Product

Resources

About

Polyphenols restore endothelial function in DOCA-salt hypertension: Role of endothelin-1 and NADPH oxidase

Cited by 92 publications

References 58 publications

Endothelium-Dependent Vasodilator Effects of Peroxisome Proliferator-Activated Receptor β Agonists via the Phosphatidyl-Inositol-3 Kinase-Akt Pathway

Endothelium-Dependent Vasodilator Effects of Peroxisome Proliferator-Activated Receptor β Agonists via the Phosphatidyl-Inositol-3 Kinase-Akt Pathway

Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

Contact Info

Product

Resources

About

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review