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The effectiveness of Methylobacterium symbioticum in maize and strawberry plants was measured under different doses of nitrogen fertilisation. The biostimulant effect of the bacteria was observed in maize and strawberry plants treated with the biological inoculant under different doses of nitrogen fertiliser compared to untreated plants (control). It was found that bacteria allowed a 50 and 25% decrease in the amount of nitrogen applied in maize and strawberry crops, respectively, and the photosynthetic capacity increased compared with the control plant under all nutritional conditions. A decrease in nitrate reductase activity in inoculated maize plants indicated that the bacteria affects the metabolism of the plant. In addition, inoculated strawberry plants grown with a 25% reduction in nitrogen had a higher concentration of nitrogen in leaves than control plants under optimal nutritional conditions. Again, this indicates that Methylobacterium symbioticum provide an additional supply of nitrogen., (© 2023. The Author(s).)

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-β (Aβ) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aβ is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins., Methods: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA., Results: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS., Discussion: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral β-amyloidosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonaterra-Pastra, Benítez, Pancorbo, Rodríguez-Luna, Vert, Rovira, Freijo, Tur, Martínez-Zabaleta, Cardona Portela, Vera, Lebrato-Hernández, Arenillas, Pérez-Sánchez, Domínguez-Mayoral, Fàbregas, Mauri, Montaner, Sánchez-Quesada and Hernández-Guillamon.)

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer's disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.

Strigolactones (SLs) are important ex-planta signalling molecules in the rhizosphere, promoting the association with beneficial microorganisms, but also affecting plant interactions with harmful organisms. They are also plant hormones in-planta, acting as modulators of plant responses under nutrient-deficient conditions, mainly phosphate (Pi) starvation. In the present work, we investigate the potential role of SLs as regulators of early Pi starvation signalling in plants. A short-term pulse of the synthetic SL analogue 2'-epi-GR24 promoted SL accumulation and the expression of Pi starvation markers in tomato and wheat under Pi deprivation. 2'-epi-GR24 application also increased SL production and the expression of Pi starvation markers under normal Pi conditions, being its effect dependent on the endogenous SL levels. Remarkably, 2'-epi-GR24 also impacted the root metabolic profile under these conditions, promoting the levels of metabolites associated to plant responses to Pi limitation, thus partially mimicking the pattern observed under Pi deprivation. The results suggest an endogenous role for SLs as Pi starvation signals. In agreement with this idea, SL-deficient plants were less sensitive to this stress. Based on the results, we propose that SLs may act as early modulators of plant responses to P starvation., (© 2020 John Wiley & Sons Ltd.)

Background and Purpose: To investigate the efficacy and safety of mechanical thrombectomy in patients with acute ischemic stroke according to the oral anticoagulation medication taken at the time of stroke onset., Materials and Methods: A retrospective multicenter study of prospectively collected data based on data from the registry the Madrid Stroke Network was performed. We included consecutive patients with acute ischemic stroke treated with mechanical thrombectomy and compared the frequency of intracranial hemorrhage and the modified Rankin Scale (mRS) score at 3 months according to anticoagulation status., Results: The study population comprised 502 patients, of whom 389 (77.5%) were not anticoagulated, 104 (20.7%) were taking vitamin K antagonists, and 9 (1.8%) were taking direct oral anticoagulants. Intravenous thrombolysis had been performed in 59.8% and 15.0% of non-anticoagulated and anticoagulated patients, respectively. Rates of intracranial hemorrhage after treatment were similar between non-anticoagulated and anticoagulated patients, as were rates of recanalization. After 3 months of follow-up, the mRS score was ≤2 in 56.3% and 55.7% of non-anticoagulated and anticoagulated patients, respectively (P=NS). Mortality rates were similar in the two groups (13.1%and12.4%, respectively). Among anticoagulated patients, no differences were found for intracranial bleeding, mRS score, or mortality rates between patients taking vitamin K antagonists and those taking direct oral anticoagulants., Conclusions: Mechanical thrombectomy is feasible in anticoagulated patients with acute ischemic stroke. The outcomes and safety profile are similar to those of patients with no prior anticoagulation therapy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Nonagenarians are under-represented in thrombolytic trials for acute ischemic stroke (AIS). The effectiveness of intravenous thrombolytics in nonagenarians in terms of safety and outcome is not well established., Materials and Methods: We used a multinational registry to identify patients aged 90 years or older with good baseline functional status who presented with AIS. Differences in outcomes-disability level at 90 days, frequency of symptomatic intracerebral hemorrhage (sICH), and mortality-between patients who did and did not receive thrombolytics were assessed using multivariable logistic regression, adjusted for prespecified prognostic factors. Coarsened exact matching (CEM) was utilized before evaluating outcome by balancing both groups in the sensitivity analysis., Results: We identified 227 previously independent nonagenarians with AIS; 122 received intravenous thrombolytics and 105 did not. In the unmatched cohort, ordinal analysis showed a significant treatment effect (adjusted common odds ratio [OR]: .61, 95% confidence interval [CI]: .39-.96). There was an absolute difference of 8.1% in the rate of excellent outcome in favor of thrombolysis (17.4% versus 9.3%; adjusted ratio: .30, 95% CI: .12-.77). Rates of sICH and in-hospital mortality were not different. Similarly, in the matched cohort, CEM analysis showed a shift in the primary outcome distribution in favor of thrombolysis (adjusted common OR: .45, 95% CI: .26-.76)., Conclusions: Nonagenarians treated with thrombolytics showed lower stroke-related disability at 90 days than those not treated, without significant difference in sICH and in-hospital mortality rates. These observations cannot exclude a residual confounding effect, but provide evidence that thrombolytics should not be withheld from nonagenarians because of age alone., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Strigolactones are multifunctional molecules involved in several processes outside and within the plant. As signalling molecules in the rhizosphere, they favour the establishment of arbuscular mycorrhizal symbiosis, but they also act as host detection cues for root parasitic plants. As phytohormones, they are involved in the regulation of plant architecture, adventitious rooting, secondary growth and reproductive development, and novel roles are emerging continuously. In the present study, the possible involvement of strigolactones in plant defence responses was investigated. For this purpose, the resistance/susceptibility of the strigolactone-deficient tomato mutant Slccd8 against the foliar fungal pathogens Botrytis cinerea and Alternaria alternata was assessed. Slccd8 was more susceptible to both pathogens, pointing to a new role for strigolactones in plant defence. A reduction in the content of the defence-related hormones jasmonic acid, salicylic acid and abscisic acid was detected by high-performance liquid chromatography coupled to tandem mass spectrometry in the Slccd8 mutant, suggesting that hormone homeostasis is altered in the mutant. Moreover, the expression level of the jasmonate-dependent gene PinII, involved in the resistance of tomato to B. cinerea, was lower than in the corresponding wild-type. We propose here that strigolactones play a role in the regulation of plant defences through their interaction with other defence-related hormones, especially with the jasmonic acid signalling pathway., (© 2013 BSPP AND JOHN WILEY & SONS LTD.)

Introduction: Our aim was to analyze our clinical experience with dabigatran etexilate in secondary stroke prevention., Methods: We retrospectively included patients starting dabigatran etexilate for secondary stroke prevention from March 2010 to December 2012. Efficacy and safety variables were registered., Results: 106 patients were included, median follow-up of 12 months (range 1-31). Fifty-six females (52.8%), mean age 76.4 (range 50-95, SD 9.8), median CHADS2 4 (range 2-6), CHA2DS2-VASc 5 (range 2-9), and HAS-BLED 2 (range 1-5). Indication for dabigatran etexilate was ischemic stroke in 101 patients and acute cerebral hemorrhage (CH) due to warfarin in 5 (4.7%). Dabigatran etexilate 110 mg bid was prescribed in 71 cases (67%) and 150 mg bid was prescribed in the remaining. Seventeen patients (16%) suffered 20 complications during follow-up. Ischemic complications (10) were 6 transient ischemic attacks (TIA), 3 ischemic strokes, and 1 acute coronary syndrome. Hemorrhagic complications (10) were CH (1), gastrointestinal bleeding (6), mild hematuria (2), and mild metrorrhagia (1), leading to dabigatran etexilate discontinuation in 3 patients. Patients with previous CH remained uneventful. Three patients died (pneumonia, congestive heart failure, and acute cholecystitis) and 9 were lost during follow-up., Conclusions: Dabigatran etexilate was safe and effective in secondary stroke prevention in clinical practice, including a small number of patients with previous history of CH.

Background and Objective: Patients admitted to Cardiology and Cardiac Surgery Departments have an increased risk of ischemic stroke (IS). We analyzed clinical characteristics, quality of neurological care and mortality of in-hospital strokes (IHS) in these departments., Patients and Method: Prospective registry of in-hospital ISs in Cardiology and Cardiac Surgery in 13 Spanish hospitals during 2008. Demographic, clinical and therapeutic data as well as mortality and functional evolution were recorded., Results: 73 patients were included. Mean age was 72±11.6 years. 75.4% of IS were cardioembolic. Special risk factors were presence of cardiac sources of embolism (86.3%), prior withdrawal of antithrombotic treatment (22%) and invasive procedures (65.7%). First neurological assessment was done in the first 3hours in 49.5% and beyond 24hours from IS onset in 20.5%. Ten patients were treated with intravenous thrombolysis, which was not possible in 8 patients because of the delay in calling the neurologist. Most frequent reasons for exclusion from thrombolytic therapy were recent major surgical procedures (33.3%) and anticoagulant therapy (38%). Three-month mortality was 15% and only 53.7% were functionally independent. Patients treated with thrombolysis had a better evolution (87.5% of independent patients, p=0.04)., Conclusions: IS in Cardiology and Cardiac Surgery are mostly cardioembolic strokes and produce a high proportion of dependent patients. Patients treated with thrombolysis had a better evolution. Delays in contacting the neurologist led to exclusion from treatment an important proportion of patients who met thrombolysis criteria., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Red wine polyphenols (RWPs) have been reported to exert beneficial effects in preventing cardiovascular diseases, such as hypertension. We studied the effects of chronic treatment with RWPs and apocynin, an inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, on blood pressure, endothelial function, and oxidative status in deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Rats were administered RWPs (40 mg/kg) or apocynin (33 microg/kg) daily by gavage for 5 weeks. Plasma catechin levels were detected only after RWP treatment. RWPs and apocynin prevented both the increase in systolic blood pressure and the proteinuria induced by DOCA-salt. Plasma malonyldialdehyde levels, urinary iso-prostaglandin F(2alpha) excretion, aortic superoxide production, and aortic NADPH oxidase activity were found to be increased in animals of the DOCA group. RWP and apocynin treatments reduced these parameters in DOCA-salt rats, having no effect on control rats. However, only RWPs reduced the increase in plasma endothelin-1 (ET-1) levels and aortic p22(phox) gene overexpression found in DOCA-salt animals. RWPs and apocynin also improved the blunted endothelium-dependent relaxation response to acetylcholine in noradrenaline-precontracted aortic rings. All these results suggest that chronic treatment with RWPs prevents hypertension and vascular dysfunction. RWPs prevent vascular oxidative stress by inhibiting NADPH oxidase activity and/or by reducing ET-1 release.

Background and Objective: Several studies have found that chronic treatment with the dietary flavonoid quercetin lowers blood pressure and restores endothelial dysfunction in hypertensive animal models. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression and activity, and reduced reactive oxygen species might be involved in the improvement of endothelial function induced by quercetin in spontaneously hypertensive rats (SHR)., Design and Methods: Male SHR and Wistar-Kyoto (WKY) rats (5 weeks old) were treated with quercetin (10 mg/kg) or vehicle for 13 weeks. Changes in vascular expression of eNOS, caveolin-1 and p47 were analysed by Western blot, eNOS activity by conversion of [H]arginine to L-[H]citrulline, and NADPH oxidase activity by NADPH-enhanced chemoluminescence of lucigenin., Results: In SHR, quercetin reduced the increase in blood pressure and heart rate and enhanced the endothelium-dependent aortic vasodilation induced by acetylcholine, but had no effect on the endothelium-independent response induced by nitroprusside. However, quercetin had no effect on endothelium-dependent vasoconstriction and aortic thromboxane B2 production. Compared to WKY, SHR showed upregulated eNOS and p47 protein expression, downregulated caveolin-1 expression, increased NADPH-induced superoxide production but, paradoxically, eNOS activity was reduced. Chronic quercetin treatment prevented all these changes in SHR. In WKY, quercetin had no effect on blood pressure, endothelial function or the expression or activity of the proteins analysed., Conclusions: Enhanced eNOS activity and decreased NADPH oxidase-mediated superoxide anion (O2) generation associated with reduced p47 expression appear to be essential mechanisms for the improvement of endothelial function and the antihypertensive effects of chronic quercetin.

The aim of the present study was to analyze whether consumption of a fiber-supplemented diet containing 3.5% Plantago ovata husks prevented many of the abnormalities clustered in the metabolic syndrome, including obesity, dyslipidemia, hypertension and endothelial dysfunction. For this purpose, obese Zucker rats, a model of type 2 diabetes, and their lean littermates were studied. Rats consumed a standard control diet or that diet supplemented with 3.5% P. ovata husks for 25 wk. Body weights were measured weekly. Systolic blood pressure (SBP) was measured monthly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, FFAs, glucose, insulin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) were determined, and studies on vascular function were performed using aortic rings. Rats fed the P. ovata husk-supplemented diet had a significantly reduced body weight gain compared with those fed the standard diet. Decreased endothelium-dependent relaxation in response to acetylcholine (ACh) by aortic rings from obese Zucker rats was improved in those fed the fiber-supplemented diet. The greater SBP, higher plasma concentrations of triglycerides, total cholesterol, FFA, glucose, insulin, and TNF-alpha, and the hypoadinectinemia that occurred in obese Zucker rats that consumed the control diet were significantly improved in those fed the fiber-supplemented diet. We conclude that intake of a P. ovata husk-supplemented diet prevents endothelial dysfunction, hypertension, and obesity development, and ameliorates dyslipidemia and abnormal plasma concentrations of adiponectin and TNF-alpha in obese Zucker rats.

The aim of this study was to analyze the effects of the isoflavones genistein and daidzein, and the mammalian estrogen 17beta-estradiol on endothelial function in isolated aortic rings from male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Relaxation to acetylcholine on precontracted rings was impaired and endothelium-dependent contraction to acetylcholine in aortic rings was increased in SHR compared with WKY. Aortic NADPH-stimulated O(2)(-) release and prostaglandin (PG)H(2) production evoked by acetylcholine were increased, whereas nitric-oxide synthase activity was reduced in SHR versus WKY. Genistein, daidzein, or 17beta-estradiol enhanced the relaxant response to acetylcholine and decreased the endothelium-dependent vasoconstrictor responses to acetylcholine in SHR, but not in WKY, and these effects were not modified by the estrogen receptor antagonist ICI 182,780 (7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)-sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol). Moreover, isoflavones enhanced nitric-oxide (NO) synthase activity and inhibited NADPH-stimulated O(2)(-) roduction and endothelial release of PGH(2). The contractions induced by the TP receptor agonist U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2alpha)) in denuded aortic rings were inhibited by genistein, daidzein, and 17beta-estradiol in both strains. In conclusion, the isoflavones genistein and daidzein and 17beta-estradiol restore endothelial function in male SHR through estrogen receptor-independent mechanisms. Increased NO production and protection of NO from O(2)(-)-driven inactivation might be involved in the improvement of vascular relaxation to acetylcholine in aortic rings from SHR. Moreover, isoflavones and 17beta-estradiol inhibited aortic endothelium-dependent contraction to acetylcholine in SHR by reducing the endothelial PGH(2) release and its vasoconstrictor response.

In the present study, the effects of the bioflavonoid chrysin (5,7-dihydroxyflavone) were analysed on nitric oxide (NO) production from vascular endothelium. In aortic rings, incubation with chrysin or acetylcholine (both at 10 microM) increased L-NAME-sensitive endothelial NO release as measured using the fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2 DA). Moreover, chrysin increased cGMP accumulation only in aortic rings with endothelium. However, at this concentration, chrysin had no effect either on basal or on NADPH-stimulated vascular superoxide production. Moreover, at this low concentration, chrysin, similar to acetylcholine, induced aortic relaxation, which was abolished by both endothelial deprivation and NO synthase inhibition. Endothelium-dependent relaxation induced by chrysin was unaltered by removal of extracellular calcium and incubation with the intracellular calcium chelator BAPTA, while the phosphatidylinositol (PI)-3 kinase inhibitor wortmannin suppressed the endothelial dependence. In conclusion, chrysin stimulated NO release from endothelial cells leading to vascular cGMP accumulation and subsequent endothelium dependent aortic relaxation. Chrysin-stimulated NO release is calcium independent and possibly mediated via PI3-kinase.

In the present study, the effects of the bioflavonoid chrysin (5,7-dihydroxyflavone) were analyzed on the perfusion pressure of isolated mesenteric vascular bed. The vasorelaxant effects of chrysin were more potent on intact endothelium than on denuded vessels. This endothelium-dependent response induced by chrysin was inhibited in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME), KCl, tetraethylammonium (TEA), BaCl(2), TEA plus L-NAME, and ouabain plus BaCl(2), while incubations with indomethacin and glibenclamide did not modify the response induced by this bioflavonoid. Neither gap junction inhibition with carbenoxolone nor epoxyeicosatrieconic acid synthesis inhibition with sulfaphenazole (selective CYP 2C/3A inhibitor) or 7-ethoxyresorufin (selective CYP 1A inhibitor) inhibited the chrysin-induced relaxation. Moreover, chrysin increased L-NAME-sensitive cGMP accumulation in intact vascular mesenteric preparation. In conclusion, chrysin shows vasodilator effects on resistance vessels, which depend partially on the functional endothelium and appear to be related to the NO/cGMP pathway and, possibly to the release of endothelium-derived hyperpolarizing factor., (Copyright 2004 S. Karger AG, Basel.)

Chronic oral quercetin exerts antihypertensive effects in spontaneously hypertensive rats (SHR). In the present study, the vasodilator effects of the flavonoid quercetin and its main metabolite isorhamnetin were analysed in isolated thoracic aorta, iliac artery and on the isolated perfused mesenteric resistance vascular bed from SHR and normotensive Wistar Kyoto rats (WKY). In noradrenaline-precontracted vessels from SHR there was an inverse correlation between the relaxant potency (pIC50) of quercetin (4.76 +/- 0.02, 5.08 +/- 0.12, 5.30 +/- 0.18, in aorta, iliac arteries and mesentery, respectively) and isorhamnetin (4.90 +/- 0.11, 5.38 +/- 0.15 and 5.80 +/- 0.10, respectively) and the diameter of the vessel studied. Both flavonoids were more potent in endothelium-denuded aortae and iliac arteries from SHR than from normotensive WKY rats. In addition, in aortae from SHR both flavonoids restored the endothelial-dependent vasodilation. Isorhamnetin, but not quercetin, also reduced the endothelium-dependent contractile responses induced by acetylcholine. These direct vasodilator effects, together with the improvement of endothelial function, are good candidates to explain the blood pressure reduction and vascular protective effects of quercetin in animal models of hypertension and possibly in human cardiovascular diseases.