It is demonstrated that 17-[3-estradiol sulfate increases the electrical homogeneity of the myocardium as a result of reducing the differences in the duration of cardiomyocyte action potentials. Key Words: myocardium; transmembrane .potentials; estradiolOn the basis of autoradiography data it has been hypothesized that the heart is a target organ for both estrogens and androgens [7,8]. Although the cytosolic reception of estrogens predominates, it has been assumed that the membrane processes play an important role in the mechanism of action of steroid hormones [4,51.The heart of animals with transformed hormonal status (males treated with estrogens) is more resistant to arrhythmogenic factors and is more capable of spontaneous defibrillation [1,2,6]. Since it is difficult to distinguish between direct and indirect effects of estrogens on cardiomyocytes in vivo, the present study was carried out on isolated myocardial stripes. MATERIALS AND METHODSEighteen experiments were performed on isolated myocardial stripes excised from the left ventricle of guinea pig heart. The stripes were perfused with warm (33~ pH 7.3) oxygenated (95% 0,/5% CO2) Ringer solution containing (in mM): K(~I 4, NaC1 137, CaC1, 2, NaHPO 4 1.8, MgC12 2.7, NaHCO 3 1.75 g/liter, and glucose 2 g/liter. An aqueous solution of 17-[3-estradiol sulfate (10 -6 g/liter, 17-[3-ES, Sigma) was employed as an estrogen. The solution was changed every 3 min.The electrical activity of endocardial and epicardial cells was continuously recorded with a Tektronix 5103N oscilloscope, photocamera, and glass electrodes filled with 3 M KC1. The resting potential (RP), and the amplitude and duration of the action potential (AP) at 20, 50, and 80% repolarization were measured by the standard methods; the first derivative of the front of AP growth was determined.Statistical analysis was performed using PSI-PLOT software. RESULTSIn order to suppress sources of automaticity, the stripes were stimulated with a frequency of 1.4-2 Hz for 25-30 min. Under a light microscope, a microelectrode was inserted in cells of the trabecular muscles located on the endocardial surface. It was found

The use of gestagen hormones (progestogens, progestogens, progestins) in modern medicine is mainly based on their effect on the reproductive sphere of the female body, including menstrual dysfunction (luteal phase of the cycle), contraception, pregnancy support, correction of hormonal homeostasis during menopause, antitumor activity in some hormone-dependent oncological diseases. The presence of antiandrogenic properties in a number of progestogens (C21-derivatives), which have found application as antihormonal therapy for certain endocrine diseases in women (hirsutism) and for malignant neoplasms of the male genital organs, should be highlighted. The variety of influences exerted by natural gestagen hormones and their synthetic analogs on the human body also encompasses a change in their action of cardiovascular activity. Moreover, according to some authors, the heart and large vessels are the targets of the action of gestagens. It is assumed that a change in the hormonal characteristics of the female body during the normal menstrual cycle does not cause existing changes in the reactivity of the cardiovascular system. However, fluctuations in cardioactive and vasoactive parameters can be observed even with physiological differences in the level of endogenous progestogens and estrogens (menstrual cycle, pregnancy, menopause). The greatest severity of maladaptation phenomena in cardiac activity (according to the mathematical analysis of cardiointervalograms) was revealed precisely at peak concentrations of female sex hormones within the estrous cycle - in the phases of proestrus and metaestrus. During menopause and postmenopause, when the cardioprotective effect of endogenous estrogens and gestagens is significantly reduced, a violation of cardiac and vasomotor activity can be detected, often requiring hormone replacement therapy with estrogen-gestagen drugs.

Cardioprotective and antiradical activities of estrogens and their nitro derivatives are compared. Antiradical activity was observed in estradiol, ethanol estradiol, and estradiol nitrate, but not in nystranol, which exhibited antiradical properties only after acid hydrolysis. The data obtained on hearts from rats with experimental myocardial infarction show that estrogens and their nitro derivatives restrict the area of myocardial infarction due to antiischemic and/or antinecrotic activities. Key Words: antiradical activity; nitro estrogens; experimental myocardial infarctionConsiderable attention is now focused on clinical application of estrogens and their synthetic analogs for preventing and treating cardiovascular diseases not only in women, but also in men [2,6].There is evidence that natural estrogen 17~-estradiol possesses a cardioprotective effect and restricts the area of myocardial infarction (MI) [5].In this connection it is of interest to study modified synthetic estrogens carrying an ONO 2 group, potential donor of nitric oxide. These derivatives are nystranol and estradiol nitrate.Chemical structure of nystranol and estradiol nitrate suggests that they could affect the cardiovascular system more efficiently than classical estrogens due to generation of bioactive NO group.Natural estrogens have a pronounced antiradical activity [3]. There are no such data on the nitro estrogens. Bearing in mind the important role of lipid peroxidation in the pathogenesis of MI, examination of estrogen nitro derivatives for potential antiradical activity would have a practical resonance.Our aim was to compare cardioprotective and antiradical activity of estrogens and their nitro derivatives MATERIALS AND METHODSExperiments were carried out on outbred albino rats of both sexes weighing 200-300 g. Estradiol (17~-estradiol), ethanol estradiol, nystranol (9t~-oxy-1 l~-nitroxyethynylestradiol diacetate), and estradiol nitrate (17 estradiol nitrate) were injected intraperitoneally in a dose of 10 mg/kg (in 20% ethanol) one hour before coronary occlusion. MI was provoked by ligating the descendant branch of the left coronary artery immediately below the auricula [7].The effect of steroids on the size of experimental MI was assessed after 4-h coronary occlusion.Estrogens and their nitro derivatives were tested for antiradical activity in the reaction of azo-bis-isobutyronitrile-induced oxidation of isopropylbenzene (cumol) as described elsewhere [9,10]. Test substance was added to cumol in a concentration of 5• -3 M. Nystranol was hydrolyzed with 0.1 M HCI. Oxidation kinetics was assessed by oxygen consumption measured using a gasometric setup. To determine the rate constant of interaction of the inhibitor with cumol peroxide radicals (K7), the kinetic curve of oxygen absorption was plotted in the semilogarithmic scale convert-0007-4888/99/0010-1009522.00 9Kluwer Academic/Plenum Publishers

Effects of predaisolone, estradiol, and testosterone on the transport of Ca : § and the respiration induced by it in the heart and liver mitochondria of rats were studied. Prednisolone and testosterone were found to reduce the Ca-accumulating capacity of the mitochondria, the rates of ion entry and exit, and the rate of Ca2*-induced respiration. Estradiol, while inhibiting Ca 2 § transport across mitochondrial membrane, did not influence the respiration in the phase of Ca 2 § absorption, but accelerated it in the phase of ion exit. These data suggest that due to their lipophilic properties, the steroids become incorporated in the mitochondrial membrane, thereby changing its viscosity and permeability and limiting the mobility of transmitter proteins. Key Words: Ca 2 § transport; mitochondria; oxidative metabolism; steroid hormonesThe transport of Ca 2 § ions in a mitochondrion is a function extremely important for the vital activity of cells, as it is a component of their regulatory mechanisms controlling their energy-synthesizing function. It is well known that Ca 2 § ions modulate the activity of three matrix dehydrogenases regulating the Krebs' cycle [5]. The Ca-accumulating capacity of the mitochondria is known to be realized through two different mechanisms: 1) active electrophoretic absorption of Ca 2 § owing to the electric component of the proton-moving force and 2) electroneutral exit of Ca ~ § via the Na/Ca transmitter, which is particularly active in the heart and excitable tissues [5]. The energy-dependent route of Ca 2 § absorption and metabolism through the Na/Ca transmitter form a biphasic Ca cycle [6] whose disturbance may interfere with the mitochondrial energy-producing function and the mitochondrial-cytosol interactions. It was demon-