Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism
Gemma A. Figtree, MB, BMedSci*,
Huw Griffiths, MB, BSca*,
Ying-Qing Lu, PhDa*,
Carolyn M. Webb, PhDa*,
Kenneth MacLeod, PhDa* and
Peter Collins, MD, FRCP, FACC*
a Cardiac Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, London, United Kingdom
* Department of Physiology, University of Sydney, Sydney, Australia
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Figure 1 Bar graph showing the relaxing effect of genistein (10, 20 and 40 µM) on rabbit coronary artery rings with (n = 6) and without endothelium (n = 6). Rings were precontracted with K+ (30 mM). Data are expressed as percentage relaxation of contraction induced by K+ (mean ± SEM). Control indicates a time-matched equivalent volume of solvent (n = 12–14). *indicates significant differences in comparison with control; * = p < 0.05; ** = p < 0.01; *** = p < 0.001.
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Figure 2 Bar graph showing the relaxing effect of phloretin (5, 10, 20 and 40 µM) on rabbit coronary artery rings with (n = 6) and without (n = 6) endothelium. Rings were precontracted with K+ (30 mM). Data are expressed as percentage relaxation of contraction induced by K+ (mean ± SEM). Control indicates a time-matched equivalent volume of solvent (n = 12–14). *indicates significant differences in comparison with control; * = p < 0.05; *** = p < 0.001.
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Figure 3 Bar graph showing the relaxing effect of biochanin A (3, 10 and 30 µM) on rabbit coronary artery rings with (n = 6) and without endothelium (n = 6). Rings were precontracted with K+ (30 mM). Data are expressed as percentage relaxation of contraction induced by K+ (mean ± SEM). Control indicates a time-matched equivalent volume of solvent (n = 12–14). *indicates significant differences in comparison with control; * = p < 0.05; ** = p < 0.001.
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Figure 4 Original tracing demonstrating genistein (10, 20 and 40 µM)-induced relaxation in K+-contracted coronary arterial rings.
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Figure 5 Comparison of the relaxant effects of equivalent concentrations (10 µM) of genistein, phloretin and biochanin A.
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Figure 6 (a) The effect of incubation in L-NAME (L-NA), ICI 182,780 (ICI) and indomethacin (Indometh) on genistein-induced relaxation in rings with endothelium compared with control rings (no incubation) (n = 6, p > 0.05). (b) The effect of incubation in barium chloride (BaCl), glibenclamide (Gliben) and methylene blue (Methyl blue) on genistein-induced relaxation in rings without endothelium compared with control rings (no incubation) (n = 6, p > 0.05).
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Figure 7 The effect of genistein (Ge: 20 and 40 µM) (a) and zearalenone (Zea; 1 and 10 µM) (b) on the calcium concentration-dependent contraction curves in rabbit coronary arteries without endothelium compared with control. Data are expressed as percentage of maximal contraction induced by calcium in controls (mean ± SEM). *indicates significant differences in comparison with corresponding controls; * = p < 0.05; ** = p < 0.01; *** = p < 0.001.
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Figure 8 The effects of genistein on calcium current and contraction of isolated guinea-pig cardiac myocytes. (A) Averaged traces from a representative cell on repetitive step depolarizations from a holding potential of –40 mV to 0 for 400 ms. (i) Control in normal Tyrode, (ii) after 1 min stabilization in 2 µM genistein, (iii) after washout in normal Tyrode and a period of action potential stimulation under current clamp. (B) (i) Current-voltage and (ii) contraction-voltage relationships in normal Tyrode (open circle) and 2 µM genistein (solid circle) with step depolarizations of 400 ms from a holding potential of –40 mV (n = 9 unless indicated otherwise). (C) Dose-response relationships for (i) L-type calcium current and (ii) contraction after 90 s in varying concentrations of genistein (n indicated for each bar). In all cases, data are expressed as mean ± SEM. * indicates p < 0.05; ** indicates p < 0.01; *** indicates p < 0.001 compared with control.
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