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  • 1
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    Online Resource
    Abstract 529: Atorvastatin and Sildenafil Reduce Vascular Remodeling and Oxidative Stress in 2K1C-hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Hypertension Vol. 60, No. suppl_1 ( 2012-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 60, No. suppl_1 ( 2012-09)
    Abstract: Atorvastatin (ATORVA) and sildenafil (SILD) exert beneficial effects on cardiovascular diseases through their pleiotropic effects. Hypertension-induced vascular hypertrophy is associated with oxidative stress and matrix metalloproteinase (MMP) up-regulation. We evaluated the effects of ATORVA and SILD on vascular changes induced by MMPs and on oxidative stress and MMP activity in 2 kidney-1 clip (2K1C) hypertension. Sham and 2K1C rats were treated with vehicle, ATORVA (50 mg/kg), SILD (45 mg/kg) or both for 8 weeks. ATORVA, SILD, or both drugs exerted antihypertensive effects (systolic blood pressure: 148±6, 156±2, and 138±4 mmHg, respectively, vs. 200±4 mmHg in 2K1C untreated rats; P 〈 0.05). All treatments prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats (P 〈 0.05). Aortas from 2K1C rats showed higher MMP-2 levels when compared with sham and all treatments attenuated 2K1C hypertension-induced increases in MMP-2 levels (both P 〈 0.05). Increased gelatinolytic activity (20.6±0.9 vs. 13.9±1.2 A.U.; arbitrary units) co-localized with upregulated aortic MMP-2 expression (8.1±0.3 vs. 5.4±0.4 A.U.) in 2K1C vs. control rats. ATORVA, SILD, or both drugs lowered gelatinolytic activity to 14.6±0.5, 14.6±1.0 and 14.5±0.8 A.U. and lowered the aortic MMP-2 expression to 5.8±0.3, 5.9±0.5 and 5.5±0.5 A.U., respectively. However, these drugs had no in vitro effects on human recombinant MMP-2 activity (P 〉 0.05). Hypertension induced oxidative stress assessed with dihydroethidium probe (7.9±1.2 vs. 16.5±1.5 A.U. in sham vs 2K1C), which was attenuated by ATORVA, SILD or both (9.9±0.3, 10.4±1.5 and 9.6±0.6 A.U., respectively). Plasma malondialdehyde levels paralleled dihydroethidium results. Treatment with ATORVA or SILD, or both, exert antihypertensive effects and prevents 2K1C hypertension-induced vascular remodeling and oxidative stress. These effects were associated with lower MMP-2 levels possibly resulting of antioxidants effects. Our results suggest that ATORVA and SILD may prevent the vascular alterations of hypertension.Supported by FAPESP, Cnpq.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.60.suppl_1.A529
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 2
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    Abstract P423: Chronic Doxycycline Administration Inhibits Angiotensin Converting Enzyme Activity and Exerts Antioxidants Effects in Renovascular Hypertensive Rats
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Hypertension Vol. 70, No. suppl_1 ( 2017-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. suppl_1 ( 2017-09)
    Abstract: Doxycycline (Dox), an established matrix metalloproteinase (MMP) inhibitor, and angiotensin-converting enzyme inhibitors (ACEi) present beneficial cardiovascular effects which could be consequence of their antioxidants properties. Furthermore, some evidences have shown other biochemical similarities between Dox and ACEi suggesting that Dox could also inhibit ACE and ACEi directly interact with MMPs and inhibit these proteases. Supporting this idea, Dox is able to chelate divalent metals, such as calcium and zinc, which are essential for the ACE activity. In this regard, we hypothesized that Dox inhibits ACE activity in hypertensive rats which leads to a reduction in ROS production and decrease hypertension. Sham-operated or 2K1C hypertensive rats were treated with Dox (30 mg/Kg/day) or water for 4 weeks. Systolic blood pressure (SBP) was monitored weekly. Dox treatment reduced SBP in 2K1C rats from 200±12 mmHg to 158±8 mmHg (P 〈 0.05). In addition, Dox treatment attenuated reactive oxygen species (ROS) levels in hypertensive animals measured by lucigenin chemiluminescense (in RLU/mg of aorta: from 711±1.0 to 377±93; P 〈 0.05). ACE activity in aorta was increased in untreated 2K1C rats (22±0.8 nmols/min/g) when compared with the Sham group (12±1.0 nmols/min/g; P 〈 0.05) and Dox treatment was able to reduce ACE activity in 2K1C rats (15±2.0 nmols/min/g; P 〈 0.05). To evaluate whether Dox inhibits ACE activity in vitro , aortic tissues from 2K1C rats were incubated with Dox or Captopril (a known ACEi ). Dox in vitro did not affect ACE activity while captopril inhibited 80% of its activity. To verify whether Dox could inhibit ACE activity in vivo , an acute assay was performed with different doses of angiotensin I (in μg/Kg: 0.03, 0.3 and 3), after the single administration of Dox or saline (i.p.). Angiotensin I infusion increased mean arterial pressure dose-dependently and Dox pretreatment did not attenuated these increases significantly (P 〉 0.05) as Captopril.Taken together, these results show that chronic treatment with Dox inhibits ACE activity in aorta of 2K1C rats, which contribute to ROS reduction and SBP attenuation. However, the mechanism by which Dox inhibits ACE activity needs further investigation.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.70.suppl_1.p423
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2094210-2
    detail.hit.zdb_id: 423736-5
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  • 3
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    Abstract 301: Nebivolol Attenuates Prooxidant and Profibrotic Mechanisms and Decreases Vascular Remodeling in Renovascular Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Hypertension Vol. 62, No. suppl_1 ( 2013-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. suppl_1 ( 2013-09)
    Abstract: Nebivolol and metoprolol are β1-adrenergic receptor blockers with different properties. We hypothesized that nebivolol, but not metoprolol, could attenuate prooxidant and profibrotic mechanisms of hypertension vascular remodeling. Hypertension was induced in male Wistar rats by clipping the left renal artery. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (Nebi 10 mg/kg/day), metoprolol (Meto 20 mg/kg/day) or vehicle for four weeks. Systolic blood pressure was monitored weekly. Morphologic changes in the aortic wall were studied in picrosirius red sections. Aortic NAD(P)H activity was evaluated by luminescence. Nitrotyrosine staining was evaluated to assess peroxynitrite formation by immunohistochemistry. TGF-β and matrix metalloproteinase-9 (MMP-9) levels were determined by immunofluorescence, and p-ERK 1/2 expression by western blotting. Both β1-receptor antagonists exerted very similar antihypertensive effects (156 ± 8 mmHg and 151 ± 9 mmHg, respectively, versus 206 ± 7 mmHg in hypertensive controls; both P 〈 0.05). However, while metoprolol had no significant effects, nebivolol significantly (all P 〈 0.05) attenuated vascular collagen surface (237944 ± 59567, 69784 ± 17686, 183215 ± 30338 μm2, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), attenuated hypertension-induced increases in aortic NAD(P)H oxidase activity (253887 ± 13712, 143765 ± 15642, and 232465 ± 14352 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in nitrotyrosine levels (166.3 ± 2.9, 145.3 ± 1.5, 172.1 ± 7.3 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in TGF-β upregulation (7.2 ± 0.12, 6.5 ± 0.03, 7.0 ± 0.3 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups) and in MMP-9 levels (18.27 ± 0.8, 12.73 ± 0.4, 15.76 ± 1.4 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). No effects on p-ERK 1/2 expression were found with both drugs (P 〉 0.05) (1.0 ± 0.16, 0.92 ± 0.15, 0.87 ± 0.37 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). These results show for the first time that nebivolol, but not metoprolol, attenuates prooxidant and profibrotic mechanisms involving TGF-β and MMP-9, which promote vascular remodeling in hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.62.suppl_1.A301
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2094210-2
    detail.hit.zdb_id: 423736-5
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  • 4
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    Abstract 265: Chronic Treatment with Nebivolol Attenuates the Vascular Changes in the 2-Kidney, 1-Clip Model of Renovascular Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Hypertension Vol. 60, No. suppl_1 ( 2012-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 60, No. suppl_1 ( 2012-09)
    Abstract: Nebivolol (Nebi) is a β-1 receptor antagonist with vasodilator and antioxidant properties. Matrix metalloproteinases (MMPs) are enzymes involved in cardiovascular remodeling, and MMP upregulation has been associated with increased reactive oxygen species (ROS). Because vascular remodeling is associated with increased ROS and MMPs, it is possible that Nebi reverses the increased MMP levels and vascular remodeling associated with 2K-1C hypertension through its antioxidant activity. Hypertension was induced in male Wistar rats by clipping the left renal artery. Six weeks after surgery, hypertensive and sham rats were treated with Nebi (10 mg/kg/day), metoprolol (Meto; 20 mg/kg/day) or vehicle for four weeks. Systolic blood pressure (SBP) was monitored weekly by tail-cuff plethysmography. Structural changes of the aortic wall were studied in hematoxylin/eosin sections. MMPs levels and activity were determined by zymography and in situ zymography. NADPH oxidase activity and ROS production were evaluated by luminescence and dihydroethidium. Similar reductions in SBP were found with both Meto or Nebi treatments (156 ± 8 mmHg and 151 ± 9 mmHg, respectively, versus 206 ± 7 mmHg in hypertensive controls; both P 〈 0.05). However, only Nebi (all P 〈 0.05) reversed aortic hypertrophy (aortic cross sectional area x 10 4 = 89±5, 68±3, and 80±8 μm 2 , respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), the increases in aortic MMP-2 levels (0.18±0.04, 0.07±0.02, and 0.12±0.06 arbitrary units; AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in aortic MMP activity (21071±700, 16217±818, and 18848±1396, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in aortic NADPH oxidase activity (253887±13712, 143765±15642, and 232465±14352 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups) and in aortic ROS levels (8057±800, 4400±480, and 6230±1190 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). No significant differences were found in the Sham groups. Our results suggest that lower vascular NADPH oxidase may explain, at least in part, the attenuation of oxidative stress and vascular remodeling associated with Nebi.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.60.suppl_1.A265
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 2094210-2
    detail.hit.zdb_id: 423736-5
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  • 5
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    A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Topiramate for the Treatment of Compulsive Buying Disorder
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of Clinical Psychopharmacology Vol. 40, No. 2 ( 2020-3), p. 186-190
    Details
    In: Journal of Clinical Psychopharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 2 ( 2020-3), p. 186-190
    Abstract: Topiramate is an anticonvulsant that has shown promise as a pharmacological agent for the treatment of addictive disorders, including compulsive buying disorder (CBD). The aim of the present study was to examine the efficacy of topiramate in the treatment of CBD and its associated characteristics using a 12-week randomized, double-blind, placebo-controlled design. Methods Fifty patients seeking treatment of CBD who met the inclusion criteria were randomly assigned to either the experimental group (n = 25) or the control group (n = 25). Both groups received 4 sessions of psychoeducation. Results Forty-four participants completed the follow-up with no differences in the rate of dropout between groups. There were no differences between participants who received topiramate or placebo in reducing CBD symptoms assessed by the primary outcome scale (Yale-Brown Obsessive-Compulsive Scale – Shopping Version). However, participants who received topiramate were significantly more likely to show clinical improvement when assessed by a secondary outcome measure, the Compulsive Buying Follow-Up Scale. In addition, there was a trend among participants who received topiramate to report improvements in aspects of hoarding and impulsivity compared with the control group. There were significant improvements in comorbid depression and social adjustments over time, but no group × time interaction was found. Conclusions The results do not provide support for the use of topiramate in the treatment of CBD. Future investigation with larger and representative samples and longer follow-up period are needed.
    Type of Medium: Online Resource
    ISSN: 1533-712X , 0271-0749
    URL: Article
    DOI: 10.1097/JCP.0000000000001183
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 604631-9
    detail.hit.zdb_id: 2057059-4
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  • 6
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    Evaluation of Links Between High-Density Lipoprotein Genetics, Functionality, and Aortic Valve Stenosis Risk in Humans
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 34, No. 2 ( 2014-02), p. 457-462
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 2 ( 2014-02), p. 457-462
    Abstract: Studies have shown that high-density lipoprotein (HDL)–raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL metabolism is unknown. Approach and Results— A total of 1435 single nucleotide polymorphisms in genes associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5, SCARB1, LIPC, CETP, LCAT, LIPG, APOC4 , and PLTP ) were genotyped in 382 patients with echocardiography-confirmed AVS (aortic jet velocity ≥2.5 m/s) and 401 controls. After control for multiple testing, none of the genetic variants showed a positive association with case/control status (adjusted P ≥0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre–β-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were measured in apolipoprotein B–depleted serum samples from 86 patients with and 86 patients without AVS. Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ATP-binding cassette A-1 expression by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1–mediated efflux. None of these parameters were different between cases and controls. However, compared with patients without coronary artery disease, sera from patients with coronary artery disease had lower HDL cholesterol levels, scavenger receptor class B type 1–mediated efflux, and HDL size ( P ≤0.003), independently of the presence or absence of AVS. Conclusions— Results of the present study suggest that, based on HDL genetics and HDL functionality, HDL metabolism does not seem to predict the risk of AVS. Because of our limited sample size, additional studies are needed to confirm these findings.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.113.302730
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1221433-4
    detail.hit.zdb_id: 1494427-3
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  • 7
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    Abstract 393: Chronic Nebivolol Treatment Attenuates MMP Activity and Oxidative Stress and Improves Renovascular Hypertension-induced Cardiac Hypertrophy
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Hypertension Vol. 62, No. suppl_1 ( 2013-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. suppl_1 ( 2013-09)
    Abstract: Nebivolol (Nebi) is the most selective cardiac β1-adrenergic receptor blocker and exerts antioxidant effects. Reactive oxygen species (ROS) enhance cardiac matrix metalloproteinase activity (MMPs) and contribute to hypertension-induced left ventricular hypertrophy (LVH). However, it is uncertain whether Nebi decreases MMP-2 levels and cardiac remodeling associated with hypertension as a result of its antioxidant properties. Hypertension was induced by clipping the left renal artery (2K1C). Six weeks after surgery, hypertensive and sham rats were treated with Nebi, Metoprolol (Meto) or Vehicle (by gavage) for four weeks. Systolic blood pressure (SBP) was monitored weekly by tail-cuff plethysmography. LV structural changes were studied in hematoxylin/eosin sections. MMP levels and activity were determined by immunofluorescence and in situ zymography. ROS and nitrotyrosine levels were evaluated by dihydroethidium and immunohistochemistry, respectively. Similar reduction in SBP was found with both treatments (202±5 mmHg in 2K1C+Vehicle versus 161±19 and 162±18 mmHg in 2K1C Nebi or Meto groups, respectively; P 〈 0.05). Both treatments reduced LV remodeling and ROS formation (P 〈 0.05). Both drugs decreased nitrotyrosine levels (3.9±0.2, 2.3±0.3, and 2.4±0.3 arbitrary units, respectively in 2K1C+vehicle, 2K1C+Meto, and 2K1C+Nebi groups, respectively; P 〈 0.05). Increased MMP-2 levels (16.0±2.0 versus 7.0±0.9 arbitrary units; P 〈 0.05) and activity (8.0±0.4 versus 6.0±0.1 arbitrary units; P 〈 0.05) were observed in the 2K1C+vehicle group when compared to the sham group. These alterations were normalized by both treatments (similar levels to those found in the sham group). No significant changes were observed in the sham groups. These findings suggest that different β-blockers exert important antioxidant effects that may underlie the lower LV MMP activity and cardiac remodeling in 2K1C hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.62.suppl_1.A393
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2094210-2
    detail.hit.zdb_id: 423736-5
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  • 8
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    Abstract 645: Atorvastatin and Sildenafil Reduce Oxidative Stress, MMP-2 And MMP-9 Levels, TGF-beta Expression and Prevent Vascular Remodeling in 2K1C-hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Hypertension Vol. 62, No. suppl_1 ( 2013-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. suppl_1 ( 2013-09)
    Abstract: Hypertension-induced vascular remodeling is associated with oxidative stress, and matrix metalloproteinase (MMP) and TGF (transforming growth factor)-beta up-regulation. Atorvastatin (ATORVA) and sildenafil (SILD) exert pleiotropic effects that may result in cardiovascular protection. We evaluated the effects of ATORVA and SILD alone or in association on oxidative stress, MMPs and TGF-beta up-regulation, and vascular hypertrophy induced by 2 kidney-1 clip (2K1C) hypertension. Sham and 2K1C rats were orally treated with vehicle, ATORVA (50 mg/kg), SILD (45 mg/kg) or both for 8 weeks. ATORVA, SILD, or both drugs exerted antihypertensive effects (systolic blood pressure: 148±7, 156±5, and 138±4 mmHg, respectively, vs. 207±4 mmHg in 2K1C untreated rats; P 〈 0.05). All treatments prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats (P 〈 0.05). Hypertension increased NADPH oxidase activity when compared with control groups and the treatments reduced oxidative stress. Aortas from 2K1C rats showed higher MMP-2 levels when compared with sham (0.399±0.06 vs. 0.173±0.05 A.U.) and all treatments attenuated 2K1C hypertension-induced increases in MMP-2 levels (ATORVA: 0.191±0.04; SILD: 0.136±0.05; ATORVA+SILD: 0.173±0.03; P 〈 0.05). However, these drugs had no in vitro effects on human recombinant MMP-2 activity (P 〉 0.05). Moreover, 2K1C rats showed higher MMP-9 (12.64±0.86 vs. 8.70±0.92) and TGF-beta expression (14.25±0.97 vs. 9.07±1.67) compared with sham groups. All treatments prevented 2K1C hypertension-induced increases in these pro-fibrotic factors. Treatment with ATORVA or SILD, or both, exerted antihypertensive effects and prevented 2K1C hypertension-induced vascular remodeling through antioxidant and anti-fibrotic mechanisms. Our results suggest that ATORVA and SILD may prevent the vascular alterations of hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.62.suppl_1.A645
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2094210-2
    detail.hit.zdb_id: 423736-5
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