Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism

Figtree, Gemma A.; Griffiths, Huw; Lu, Yumao; Webb, Carolyn; MacLeod, Kenneth T.; Collins, Peter

doi:10.1016/s0735-1097(00)00645-8

Cited by 113 publications

(84 citation statements)

References 39 publications

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“…Formononetin inhibits the contraction induced by KCl in Krebs solution and CaCl 2 in high-K + depolarization medium, suggesting that formononetin may inhibit VDCC. This is in accordance with some previous findings [38] .…”

Section: Discussionsupporting

confidence: 94%

“…Opening of K + channels leads to membrane potential hyperpolarization and closure of voltage-dependent channels, which decreases Ca 2+ entry and causes vasodilation [37] . In our experiments, propranolol, glibenclamide, tetraethylammonium and BaCl 2 did not affect the endothelium-independent relaxant response to formononetin in rat mesenteric arteries, suggesting that the K + channels and β-adrenoceptors are not involved in the vascular relaxation processes, which is in accordance with the previous findings that K + channel inhibitors did not affect the relaxation of genistein and zearalanone, two phytoestrogens, in rabbit coronary arteries [38] . By contrast, Wu et al proposed that formononetin caused opening of iberiotoxin-sensitive Ca 2+ -activated K + channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K + channels in rat aorta [9] .…”

Section: Discussionsupporting

confidence: 93%

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Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Sun

Cao

2011

Acta Pharmacol Sin

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Aim: To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo. Methods: Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats. Results: Formononetin (1-300 μmol/L) elicited relaxation in arteries of the five regions that were pre-contracted by KCl (60 mmol/L), U46619 (1 μmol/L) or phenylephrine (10 μmol/L). The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME (100 μmol/L). Under conditions of endothelium denudation, formononetin (10, 30, and 100 μmol/L) inhibited the contraction induced by KCl and that induced by CaCl 2 in Ca 2+ -free depolarized medium. In the absence of extracellular Ca 2+ , formononetin (10, 30, and 100 μmol/L) depressed the constriction caused by phenylephrine (10 μmol/L), but did not inhibit the tonic contraction in response to the addition of CaCl 2 (2 mmol/L). The contraction caused by caffeine (30 mmol/L) was not inhibited by formononetin (100 μmol/L). Formononetin (10 and 100 μmol/L) reduced the change rate of Ca 2+ -fluorescence intensity in response to KCl (50 mmol/L). In spontaneously hypertensive rats, formononetin (5, 10, and 20 mg/kg) slowly lowered the systolic, diastolic and mean arterial pressure. Conclusion: Formononetin causes vasodilatation via two pathways: (1) endothelium-independent pathway, probably due to inhibition of voltage-dependent Ca 2+ channels and intracellular Ca 2+ release; and (2) endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Sun

Cao

2011

Acta Pharmacol Sin

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“…There is a lack of data connecting the effects of phytoestrogens with myometrial contractions in bovine. However, our observations are partly in agreement with data obtained in porcine (Lee et al, 2004) and rabbits (Figtree et al, 2000) when genistein induced relaxation in arteries in vitro. Moreover, we found that phytoestrogens can restore the proper ratio of each of the PCBs (77 at the dose 100 ng/ml, and 126 or 153, both at the dose of 10 ng/ml) on spontaneous (basal) and M) mean (± SEM) force of contractions of myometrial strips from days 19-21 of the estrous cycle (n = 5), after 48 h of incubation a-h P < 0.05; ▭ basal; ▃ OT-stimulated PGE 2 and PGF 2α secretion from bovine endometrial cells, which was disrupted by PCBs (Wrobel and Kotwica, 2005a).…”

Section: Discussionsupporting

confidence: 92%

Phytoestrogens reduce the effect of polychlorinated biphenyls on the contractility of bovine myometrium in vitro

Wróbel¹,

Kotwica²

2007

Vet. Med.

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“…This may in part be due to favorable effects on the lipid profile, as isoflavones increase high-density lipoprotein and lower lowdensity lipoprotein cholesterol levels (Cassidy et al, 1995;Anthony et al, 1998). However, isoflavones have also been shown to produce direct actions on the cardiovascular system, which may contribute toward cardioprotection (Figtree et al, 2000;Chin-Dusting et al, 2001).…”

mentioning

confidence: 99%

“…All three isoflavones directly relax arterial ring preparations in vitro (Figtree et al, 2000;Chin-Dusting et al, 2001), and genistein and daidzein have been reported to inhibit the L-type Ca 2ϩ current, I Ca,L , in isolated cardiac myocytes (Yokoshiki et al, 1996;Ogura et al, 1999). It has been assumed that this results in an overall inhibition of cell contraction, although this has not been well explored.…”

mentioning

confidence: 99%

Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

Liew

Williams²,

Collins³

et al. 2002

J Pharmacol Exp Ther

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Soy-derived isoflavones appear to possess cardioprotective properties, although the precise nature of this protection and the particular isoflavones responsible remain unclear. We hypothesized that isoflavones may differ in their cardiac actions in view of their varying affinities for the estrogen receptor and differences in ability to inhibit tyrosine kinase. We investigated the direct effects of three closely related isoflavones, genistein, daidzein, and equol (a metabolite of daidzein formed by gut microflora), on the contractile function of isolated guinea pig ventricular myocytes. Genistein (10 and 40 M) significantly increased cell shortening and the Ca 2ϩ transient (measured using indo-1). In contrast, equivalent concentrations of equol produced the opposite effect, decreasing cell shortening and the Ca 2ϩ transient, whereas daidzein was without effect. The opposing actions of genistein and equol were still observed in the presence of the specific estrogen receptor antagonist ICI 182,780 (10 M). However, the stimulatory actions of genistein were markedly reduced in the presence of the potent phosphotyrosine phosphatase inhibitor, bpV(phen). Both genistein and equol significantly inhibited the peak L-type Ca 2ϩ current. We conclude that genistein and equol affect the contractile function of ventricular myocytes in opposing ways despite a common initial action of Ca 2ϩ current antagonism. These differences occur independently of the estrogen receptor but may be partly related to the unique actions of genistein as a tyrosine kinase inhibitor. Furthermore, isoflavone metabolites, such as equol, may be more biologically active than their precursors and have a greater role in cardioprotection than previously realized.

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Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism

Abstract: This study demonstrates that phytoestrogens induce endothelium-independent relaxation of coronary arteries; the mechanism involves calcium antagonism. These mechanisms may contribute to the potential long-term cardiovascular protective effect of these substances.

Cited by 113 publications

References 39 publications

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Phytoestrogens reduce the effect of polychlorinated biphenyls on the contractility of bovine myometrium in vitro

Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

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