Inhibition of Angiotensin-Converting Enzyme by Quercetin Alters the Vascular Response to Bradykinin and Angiotensin I

Häckl, Luciane Pereira Nascimento; Cuttle, Gareth; Dovichi, Selma Sanches; Lima‐Landman, Maria Teresa R.; Nicolau, Mauro

doi:10.1159/000064341

Cited by 87 publications

(65 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to our findings, Hackl et al reported that quercetin acutely reduces the vascular responses to angiotensin I and potentiates the hypotensive responses to bradykinin, as well inhibits ACE in vitro [16]. The differences between these previous findings and those reported here may be explained by the fact that Hackl et al examined acute effects produced by a single dose of quercetin, whereas we have studied chronic effects, which may be more relevant in terms of therapeutic applications.…”

Section: Discussioncontrasting

confidence: 99%

See 1 more Smart Citation

Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro

Neto-Neves¹,

Montenegro²,

Dias‐Junior³

et al. 2010

Basic Clin Pharma Tox

View full text Add to dashboard Cite

The precise mechanisms explaining the anti-hypertensive effects produced by quercetin are not fully known. Here, we tested the hypothesis that chronic quercetin treatment inhibits the angiotensin-converting enzyme (ACE). We examined whether quercetin treatment for 14 days reduces in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetised rats. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03-10 lg ⁄ kg, by angiotensin II in doses of 0.01-3 lg ⁄ kg, and to bradykinin in doses of 0.03-10 lg ⁄ kg in anaesthetised rats pre-treated with vehicle (controls), or daily quercetin 10 mg ⁄ kg intraperitoneally for 14 days, or a single i.v. dose of captopril 2 mg ⁄ kg. Plasma ACE activity was determined by a fluorometric method. Plasma quercetin concentrations were assessed by high performance liquid chromatography. Quercetin treatment induced no significant changes in the hypertensive responses to angiotensin I and angiotensin II, as well in the hypotensive responses to bradykinin (all p > 0.05). Conversely, as expected, a single dose of captopril inhibited the hypertensive responses to angiotensin I and potentiated the bradykinin responses (all p < 0.01), while no change was found in the vascular responses to angiotensin II (all p > 0.05). In addition, although we found significant amounts of quercetin in plasma samples (mean = 206 ng ⁄ mL), no significant differences were found in plasma ACE activity in rats treated with quercetin compared with those found in the control group (50 € 6 his-leu nmol ⁄ min ⁄ mL and 40 € 7 hisleu nmol ⁄ min ⁄ mL, respectively; p > 0.05). These findings provide strong evidence indicating that quercetin does not inhibit ACE in vivo or in vitro and indicate that other mechanisms are probably involved in the antihypertensive and protective cardiovascular effects associated with quercetin.Quercetin is the most abundant flavonoid found in the human diet and several beneficial cardiovascular effects have been ascribed to it, including improved endothelial function and cardiovascular protection [1][2][3][4]. Interestingly, quercetin increased nitric oxide bioavailability, improved vascular reactivity and produced antioxidant and antihypertensive effects in different experimental models of hypertension and in clinical hypertension [1,3,[5][6][7][8][9][10][11]. However, the precise mechanisms explaining the effects produced by quercetin are poorly known.The angiotensin-converting enzyme (ACE) is a key enzyme regulating the renin-angiotensin-aldosterone system, which plays a major role in the regulation of the cardiovascular function and blood pressure [12]. In this regard, flavonoids related to quercetin have been shown to inhibit angiotensin-converting enzyme in vitro and in vivo [13][14][15]. However, there is controversy with regard to the possible effects of quercetin on ACE. While Hackl et al. reported that quercetin acutely inhibits ACE [16], Actis-Goretta et al. showed that quercetin was unable to inhibit A...

show abstract

Section: Discussioncontrasting

confidence: 99%

“…However, there is controversy with regard to the possible effects of quercetin on ACE. While Hackl et al reported that quercetin acutely inhibits ACE [16], Actis-Goretta et al…”

mentioning

confidence: 99%

Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro

Neto-Neves¹,

Montenegro²,

Dias‐Junior³

et al. 2010

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…It has been shown that losartan, an angiotensin II AT 1 receptor antagonist, attenuates cardiac hypertrophy in suprarenal abdominal aorta constricted rat [10], but has no effect on the weight gain of the ventricle during aortic arch constriction [1]. Given that quercetin can inhibit not only angiotensin converting enzyme activity [6] but also angiotensin II-mediated signal transduction in cultured cardiomyocytes [15], the antihypertrophic effect of quercetin in the present study is possible to be mediated by RAS blockage. However, quercetin had no significant effect on systemic blood pressure that is sensitive to angiotensin II.…”

Section: Discussionmentioning

confidence: 71%

Quercetin Prevents Cardiac Hypertrophy Induced by Pressure Overload in Rats

Han¹,

Jia

Kim

et al. 2009

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. Inhibition of cardiac hypertrophy leads to a significant reduction in cardiovascular mortality and morbidity. Quercetin is by far the most abundant flavonoid and believed to ameliorate cardiovascular disease. Therefore, we investigated whether quercetin supplementation could attenuate the development of cardiac hypertrophy induced by pressure overload. Three weeks after suprarenal transverse abdominal aortic constriction, heart to body weight (HW/BW) ratio increased compared to the sham group (3.40  0.06 mg/g versus 2.83  0.02 mg/g, P<0.001). The quercetin administered group showed complete inhibition of cardiac hypertrophy (2.85  0.01 mg/g, P<0.001). Malonyldialdehyde production induced by pressure overload was suppressed by quercetin. The activities of extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase, Akt and GSK-3 were significantly increased with pressure overload and attenuated by quercetin treatment. We conclude that quercetin appears to block the development of cardiac hypertrophy induced by pressure overload in rats and that these effects may be mediated through reduced oxidant status and inhibition of ERK1/2, p38 MAP kinase, Akt and GSK-3 activities.KEY WORDS: cardiac hypertrophy, pressure overload, quercetin.J. Vet. Med. Sci. 71(6): 737-743, 2009 Cardiac hypertrophy is a homeostatic response to elevated afterload that develops due to pressure or volume overload. Although cardiac hypertrophy is a compensatory response to increased wall stress in the early stage, it is followed by decompensation and ultimately leads to heart failure if the stimulus is sufficiently intense and prolonged.Several intracellular signaling pathways including mitogen-activated protein kinase (MAPK), Janus kinase/signal transducers, activators of transcription (JAK/STAT), calcineurin [16], serine/threonine kinase, Akt and its downstream target, glycogen synthase kinase-3 (GSK-3) have been implicated in mechanical stress-induced cardiac hypertrophy. These observations have led to speculation that inhibition of these hypertrophic signals may be an effective means of clinical therapy in the treatment of pathological hypertrophy and heart failure.Quercetin (3,3',4',5,7-pentahydroxyflavone) is a member of a group of naturally occurring compounds and is one of the most widely distributed bioflavonoids [5]. Several epidemiological studies have shown a significant inverse association between dietary flavonoids and long-term mortality from coronary heart disease. A very wide range of biological actions of flavonoids, including antioxidant, antiaggregant and vasodilatory effects, support the purported role of quercetin protection against cardiovascular disease [4]. Recently, it has been reported that quercetin inhibits hypertrophy of cardiomyocytes induced by angiotensin II [15]. However, there is little information about the effect of quercetin on in vivo models of cardiac hypertrophy. Therefore, the purpose of this study is to investigate whether chronic administration of an oral daily dose of quercetin...

show abstract

“…The hypotensional effect was not observed in rats with norm-tension (Marcus and Safier, 1993). Reduction in blood pressure was also noticed in the experiments with animals which were administered angiotensin (Häckl et al, 2002), as well as in the individuals with aortic valve stenosis (Jalili et al, 2006). The randomized experiments with a double-blind test proved that a daily quercetin supplementation at 730 mg for 28 days decreased systolic (by 7 mmHg) and diastolic (by 5 mmHg) blood pressure in patients with hypertension condition of the first degree.…”

Section: Hypotensional Propertiesmentioning

confidence: 62%

Quercetin – a flavonoid with a high health-promoting potential

Kulczyński¹,

Gramza‐Michałowska²,

Sidor³

2016

Nauka Przyr. Technol.

View full text Add to dashboard Cite

Summary.Flavonoids are an important group of bioactive compounds with a high antioxidant potential. Among them, one of the most common components is quercetin, belonging to the flavonols group. The main sources of quercetin are: capers, chokeberries, onions, chia seeds, honey and elderberries. This flavonoid shows a number of health-promoting properties, such as lowering blood sugar level, improving blood lipid profile, lowering blood pressure, and antimicrobial and antiplatelet activity.

show abstract

Inhibition of Angiotensin-Converting Enzyme by Quercetin Alters the Vascular Response to Bradykinin and Angiotensin I

Cited by 87 publications

References 19 publications

Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro

Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro

Quercetin Prevents Cardiac Hypertrophy Induced by Pressure Overload in Rats

Quercetin – a flavonoid with a high health-promoting potential

Contact Info

Product

Resources

About