Sherliane C Pereira1, Juliana M Parente1, Vanessa A Belo1, Atlante S Mendes1, Natália A Gonzaga2, Gabriel T do Vale2, Carla S Ceron3, José Eduardo Tanus-Santos1, Carlos R Tirapelli2, Michele M Castro4. 1. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao, Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil. 2. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao, Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil; Laboratory of Pharmacology, DEPCH, College of Nursing of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14040-902, Ribeirao Preto, Brazil. 3. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao, Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Gabriel Monteiro da Silva, 700, 37130001, Alfenas, MG, Brazil. 4. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao, Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil. Electronic address: castro@fmrp.usp.br.
Abstract
BACKGROUND AND AIMS: Increased activity of matrix metalloproteinase (MMP)-2 is observed in aortas of different models of hypertension, and its activation is directly mediated by oxidative stress. As quercetin is an important flavonoid with significant antioxidant effects, the hypothesis here is that quercetin will reduce increased MMP-2 activity by decreasing oxidative stress in aortas of hypertensive rats and then ameliorate hypertension-induced vascular remodeling. METHODS: Male two-kidney one-clip (2K1C) hypertensive Wistar rats and controls were treated with quercetin (10 mg/kg/day) or its vehicle for three weeks by gavage. Rats were then analyzed at five weeks of hypertension. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography. Aortas were used to determine MMP activity by in situ zymography and reactive oxygen species (ROS) levels by dihydroethidium. Western blot was performed to detect focal adhesion kinase (FAK) and phosphorylated-FAK levels. RESULTS: SBP was increased in 2K1C rats and only a borderline reduction in SBP was observed after treating 2K1C rats with quercetin. Cross-sectional area and the number of vascular smooth muscle cells were significantly increased in aortas of hypertensive rats, and quercetin reduced them. Quercetin reduced ROS levels in aortas of 2K1C rats and the increased activity of gelatinases in situ. However, quercetin did not affect the levels of tissue inhibitor of MMP (TIMP)-2 and did not interfere with FAK and p-FAK levels in aortas of hypertensive rats. Furthermore, different concentrations of quercetin did not directly reduce the activity of human recombinant MMP-2 in vitro. CONCLUSIONS: Quercetin reduces hypertension-induced vascular remodeling, oxidative stress and MMP-2 activity in aortas.
BACKGROUND AND AIMS: Increased activity of matrix metalloproteinase (MMP)-2 is observed in aortas of different models of hypertension, and its activation is directly mediated by oxidative stress. As quercetin is an important flavonoid with significant antioxidant effects, the hypothesis here is that quercetin will reduce increased MMP-2 activity by decreasing oxidative stress in aortas of hypertensiverats and then ameliorate hypertension-induced vascular remodeling. METHODS: Male two-kidney one-clip (2K1C) hypertensiveWistar rats and controls were treated with quercetin (10 mg/kg/day) or its vehicle for three weeks by gavage. Rats were then analyzed at five weeks of hypertension. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography. Aortas were used to determine MMP activity by in situ zymography and reactive oxygen species (ROS) levels by dihydroethidium. Western blot was performed to detect focal adhesion kinase (FAK) and phosphorylated-FAK levels. RESULTS: SBP was increased in 2K1C rats and only a borderline reduction in SBP was observed after treating 2K1C rats with quercetin. Cross-sectional area and the number of vascular smooth muscle cells were significantly increased in aortas of hypertensiverats, and quercetin reduced them. Quercetin reduced ROS levels in aortas of 2K1C rats and the increased activity of gelatinases in situ. However, quercetin did not affect the levels of tissue inhibitor of MMP (TIMP)-2 and did not interfere with FAK and p-FAK levels in aortas of hypertensiverats. Furthermore, different concentrations of quercetin did not directly reduce the activity of human recombinant MMP-2 in vitro. CONCLUSIONS:Quercetin reduces hypertension-induced vascular remodeling, oxidative stress and MMP-2 activity in aortas.
Authors: Ali Nemati; Reza Alipanah-Moghadam; Leila Molazadeh; Abbas Naghizadeh Baghi Journal: Drug Des Devel Ther Date: 2019-12-11 Impact factor: 4.162