Investigation of the negative inotropic effects of 17β‐oestradiol in human isolated myocardial tissues

• Published in: British journal of pharmacology 1996-09, Vol.119 (1), p.43-48
• Main Authors: Sitzler, Gerhard, Lenz, Olaf, Kilter, Heiko, Rosee, Karl, Böhm, Michael
• Format: Article
• Language: English
• Subjects: 17β‐Oestradiol; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Biological and medical sciences; calcium antagonism; Calcium Channel Agonists - pharmacology; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; cardiac muscle; Cell Membrane - metabolism; contractility; Depression, Chemical; Estradiol - analysis; Estradiol - pharmacology; Fundamental and applied biological sciences. Psychology; Heart; Heart - drug effects; Heart Atria - drug effects; Heart Ventricles - drug effects; Humans; In Vitro Techniques; Isradipine - pharmacology; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium - metabolism; Progesterone - pharmacology; Protein Binding - drug effects; Radioligand Assay; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15675.x

1 The aim of the present study was to evaluate the effects of 17β‐oestradiol in human myocardium. The effects of 17β‐oestradiol, progesterone and testosterone on force of contraction were investigated in electrically driven isolated atrial trabeculae and ventricular papillary muscles from human hearts in the presence and absence of Bay K 8644, a calcium channel agonist. In addition, the effects of 17β‐oestradiol, progesterone and testosterone on binding of [3H]‐PN 200 110 were assessed in membranes prepared from human ventricular myocardium. 2 17β‐Oestradiol elicited a negative inotropic effect in atrial (IC50: 7.1 μmol 1−1, confidence interval 3.8 to 13.4, n = 3) and ventricular preparations (IC50: 4.6 μmol 1−1, confidence interval 2.2 to 9.4, n = 3) as compared with solvent controls. There was no significant difference (P > 0.05) of IC50 values in the absence and presence of isoprenaline (0.01 μmol 1−1) in atrial (IC50: 10.8 μmol 1−1, confidence interval 9.1 to 12.9, n = 6) and ventricular preparations (IC50: 9.4 μmol 1−1, confidence interval 7.3 to 11.9, n = 8). 3 17β‐Oestradiol at 30 μmol 1−1 induced a significant rightward shift of the concentration‐response curves for the positive inotropic effect of Bay K 8644 in atrial preparations (EC50: 0.13 μmol 1−1, confidence interval 0.08 to 0.19, n = 6; EC50 with 17β‐oestradiol: 0.58 μmol 1−1, confidence interval 0.33 to 0.83, n = 6, P < 0.05) and ventricular preparations (EC50: 0.07 μmol 1−1, confidence interval 0.04 to 0.11, n = 8; EC50 with 17β‐oestradiol: 0.3 μmol 1−1, confidence interval 0.18 to 0.49, n = 8, P < 0.05). Testosterone, progesterone at 30 μmol 1−1 and the solvent control had no significant effect on the concentration‐response curves to Bay K 8644. 4 In membranes prepared from human ventricular myocardium the effect of 17β‐oestradiol on binding of [3H]‐PN 200 110, an antagonist at the 1,4 dihydropyridine binding site, was not different from that observed with progesterone, testosterone or solvent controls. 5 In myocardial membranes no specific oestrogen receptors were demonstrated by [3H]‐oestradiol binding studies. 6 Thus, the calcium antagonistic property of 17β‐oestradiol cannot be attributed to a direct interaction with 1, 4 dihydropyridine binding sites.