[Cardiomyocyte culture as a highly sensitive system for testing pharmacological activity of specific bradycardic agents].

Two antiarrhythmic agents were studied: verapamil and bradizole, a new bradycardic drug. It was found that both drugs exhibit a dose-dependent negative chronotropic effect on the culture of contractile cardiomyocytes of newborn rats. Bradizole showed more pronounced bradycardic properties than verapamil.

[Catecholamines in regulation of development of GnRH neurons of rat fetuses].

The contents of dopamine, serotonin, and noradrenaline in rat fetuses developing under the conditions of their deficiency induced by administration of alpha-methyl-para-tyrosine to females during 11th to 16th or 20th day of pregnancy and in fetuses, whose mothers were given saline at the same time, were determined using HPLC with subsequent electrochemical detection. Administration of alpha-methyl-para-tyrosine led to decreased levels of dopamine and noradrenaline in the areas of migration of GnRH-neurons in fetuses on days 17 and 21 of prenatal development. The concentration of serotonin remained unchanged, except in the head nasal area in males on day 21.

[Different effect of the ''recombinant'' bradykinin on the contractile activity of cultured atrial and ventricular cardiomyocytes].

The physiological activity of the "recombinant" bradykinin expressed by retrovirus recombinant pPS-3-neo (brd) was tested on cultural atrial (aCMC) and ventricular (vCMC) cardiomyocytes in newborn rats. The "recombinant" bradykinin was shown to have a chronotropic effect on aCMC and an inotropic effect on vCMC. The effects are in line with the action of the synthetic bradykinin preparation at a concentration of around 10(-15) M.

[Construction by using retrovirus vector of recombinant with synthetic bradykinin "gene" for investigations of human gene expression in mammalian cells].

The synthetic gene of bradykinin was built into the retrovirus vector pPS-3-neo under the guidance of LTR promotor, followed by pPS-3-neo (brd) vector transfection of strain 293 cells. The physiological activity of the expressed bradykinin was tested on cultured neonatal rat cardiomyocytes. The culture medium of strain 293 cells transferred by pPS-3-neo (brd) produces a positive chronotropic effect that is directly related to the time parameters of preparation of recombinant bradykinin, which are comparable with the curve of chronotropic effect of synthetic bradykinin at concentrations of 10(-17) to 10(-16) M.

[The participation of the nontraditional neuromediator nitric oxide in the mechanisms of adaptation to extreme conditions].

The investigation was performed on the medial (MMS) and lateral (LMS) magnocellular subdivisions of the hypothalamic paraventricular nuclei (HPN). The histochemical activity NO synthesizing enzyme nitric oxide synthase or NOS whose histochemical marker is NADPH-diaphorase (NADPH-D), immunocytochemical content of oxytocin (OXY), vasopressin (VP) and nucleoli sizes (squares) were studied in the mature male rats under experimental reconstruction of the both micro- and macrogravity, which are factors of the gravity field changes acting to the body during the space flight. Two experimental effects were used: B--tail suspending (imitation of the microgravity effects), C--centrifugation at 2 G (imitation of the macrogravity effects).

[Relationship between regulatory effects of serotonin and testosterone on the development of the LHRH producing system of the rat brain during the prenatal period of development].

We have performed radioimmunoassay of LHRH in rostral and septal-preoptic brain regions, as well as in mediobasal hypothalamus of male and female fetuses at day 21 of the prenatal period after the injection to pregnant females on days 11-20 of gestation of either p-chlorophenylalanine (PCPA) or of a combination of PCPA with ethane-1,2-dimethane sulfonate (EDS). Control animals received the injection of the same volume of physiological saline. In the control fetuses, both males and females, the level of LHRH in the rostral brain region was significantly lower than in the septal-preoptic region.

[Analysis of hypothalamo-hypophyseal-gonadal interrelationships in female rats in experimentally induced diabetes].

Hypothalamo-hypophyseo-gonadal system functional activity was studied in rats with streptozotocin diabetes. In intact rats concentrations of sex hormones nuclear receptors were measured in the hypothalamic preoptic-anterior, mediobasal segments and in the adenohypophysis, as were blood serum gonadotropins and sex hormones. Estradiol and progesterone were injected to ovariectomized females and LH-RH levels measured in preoptic-anterior segment of the hypothalamus, arcuate nucleus, and median eminence, as well as LH and FSH concentrations in the blood in order to detect disorders in basal and cyclic gonadotropin secretion.

[Basal and luliberin-stimulated gonadotropin secretion in ovariectomized female rats with streptozotocin-induced diabetes].

In vitro insulin effect on basal and LH-RH-stimulated gonadotropin secretion in oophorectomized female rats with streptozotocin diabetes administered estradiol as replacing hormone therapy was studied. The results were compared to those obtained after a similar incubation of adenohypophyses of oophorectomized rats and of oophorectomized rats administered estradiol. Estradiol was found to change the type of LH-RH-stimulated gonadotropin secretion in oophorectomized animals.

[A mathematical model of the physiological estrous cycle in outbred rats].

The mathematical model of the physiological estrous cycle of the laboratory rat was developed. The data on physiological concentration of the hormones, participating in the estrous cycle regulation and admittances on the growth and selection of the ovarian follicles made the base of the model. The developed system of differentiated equations allowed to reproduce quiet precisely the duration of the estrous cycle phases, to follow up the behaviour of the apparent cohort of the growing ovarian follicles during several cycles.

[Status of the hypophyseal-gonadal system in male rats with diabetes (experimental study)].

The hypophyseo-gonadal system of male rats with streptozotocin-induced diabetes was studied. The hypophyseal sensitivity to LH releasing hormone was analyzed in vitro and concentrations of sex hormone nuclear receptors in the adenohypophysis, participating in gonadotropin secretion regulation according to a negative feedback mechanism, measured. Streptozotocin injection reduced blood testosterone concentration and levels of androgen nuclear receptors in the rat hypophysis.

[Disorder of neuroendocrine regulation of sexual behavior of male rats with streptozotocin-induced diabetes].

The present paper presents studies of the sexual behavior characteristics and the associated changes of LH releasing factor and of sex hormone receptor concentrations in hypothalamic regions involved in the regulation of sexual behavior activity and hypophyseal gonadotropic function (the anterior preoptic and mediobasal regions) of rats with streptozotocin-induced diabetes. The activities of both motivational and copulative components of sex behavior of such rats were found reduced. These changes were parallelled by LH-RH reduction in the median eminence and in the synaptosomal fraction of the anterior preoptic and mediobasal regions.

[Mechanisms regulating the selective release of follicle-stimulating hormone].

Selective secretion of FSH, involving no apparent changes in LH secretion, was studied in cycling rat females in the late proestrus and early estrus stages. The preovulatory wave of LH and FSH secretion, observed in the second half of the day of proestrus was associated with elevation of the levels of nuclear estrogenic and androgenic receptors. High concentrations of both receptor types were seen during a secondary elevation of FSH secretion early in the morning in the estrus stage.

[The dependence of follicle-stimulating hormone secretion on the level of sex hormone receptors in the hypophysis and on the activity of the CNS catecholaminergic systems].

A study was made of the influence of agonists and antagonists of catecholamine action on LH and FSH secretion during the second rise of FSH secretion at the early hours of the estrous stage (E). Administration of phentolamine (a blocker of alpha-adrenoceptors) did not change the level of gonadotropins. On the contrary, haloperidol (a blocker of dopamine receptors) lowered the level of FSH at 3 o'clock of the estrous stage but made no effect on the blood concentration of LH.

[Changes in the number of estradiol and testosterone-binding sites of the hypophysis in cyclic female rats in the period of elevated follicle-stimulating hormone levels].

The level of the cytoplasmic and nuclear estradiol and testosterone receptors was investigated in the female rat hypophysis in various time-intervals of proestrus and estrus. The highest concentration of the nuclear and androgenic receptors was noted in the afternoon at the P stage during the preovulatory release of LH and FSH. After a short-term decrease in the number of the nuclear estradiol- and testosterone-binding sites at 9 and 11 p.

[Dependence of changes in the luliberin level in the synaptosomal fraction of the olfactory bulbs and various areas of the hypothalamus on the level of sexual activity in male rats].

The paper is devoted to a study of the level of LH-RH in the synaptosomal fraction of the olfactory bulbs, preoptic area and mediobasal hypothalamus, and the blood level of HL in adult male rats with sexual activity after noradrenergic denervation of the preoptic area using 6-hydroxydopamine. A neurotoxic effect of 0.1% solution of ascorbic acid, preventing 6-hydroxydopamine disintegration, was noted.

[Changes in the basal secretion of gonadotropins and the luliberin content of the hypothalamus of male rats administered catecholamines locally into the hypothalamic nuclei].

The effect of pharmacological agents (alpha-adrenoblockers alpha-adrenergic stimulators) and dopamine (DA) on LH secretion as well as the effect of local administration of noradrenaline (NA) and DA into the preoptic area (PA) or arcuate nuclei (ARC) on the LH-RH content in hypothalamic nuclei and blood LH and FSH concentration were investigated in experiments on male rats. An inhibitory effect of alpha-adrenoblockers on LH secretion was shown. This effect was reversed by the administration of stimulators DA or alpha-adrenoreceptors.

[Participation of catecholamines in the regulation of an induced wave of gonadotropins in ovariectomized rats].

The influence of various pharmacological agents (agonists or antagonists of catecholamine action) on the LH-RH content in certain discrete areas of the hypothalamus (in the preoptic area, arcuate nuclei and median eminence) and the LH and FSH levels were studied using a model of an induced wave of gonadotropins in ovariectomized rats receiving sex steroids. The administration of alpha-adrenoreceptor antagonists blocked a rise of the level of gonadotropins in the blood. The wave was restored when mesaton (alpha-adrenoreceptor stimulator) was administered in the presence of blockers.

[Synthetic tripeptide miniluliberin and its biological activity].

The effects of the synthetic decapeptide LH-RH and tripeptide mini LH-RH on LH and FSH secretion were compared. Experiments on ovariectomized female rats receiving estradiol benzoate and progesterone showed that i. v.

[Role of hypothalamic monoamines in the regulation of gonadotropin secretion].

Experiments on rats were made to examine the time course of changes in the content of dopamine, noradrenaline and serotonin in different areas of the hypothalamus during the estrous cycle and the effects of local administration of monoamines to the nuclear formations of the hypothalamus on luteinizing hormone (LH) release in intact and ovariectomized female rats. The amplitude of circadian fluctuations in the monoamine level was demonstrated to depend on the phase of the estrous cycle, with the minimal values in the preovulatory period. The differences were detected in the pattern of the response of pituitary gonadotrophics to the administration of monoamines to the hypothalamus depending on the function of the sexual glands.

[Synchronizing role of serotonin in regulating hypophyseal gonadotropic function in female rats].

The influence of local serotonin injection into the preoptic region (PR) or arcuate nucleus-medial eminence (ARN-ME) on the hypophyseal and blood luteinizing hormone (LH) level was studied in experiments on intact female rats. It was shown that a serotonin inhibiting effect is limited by a definite time interval of the proestrus phase, whereas within other phases of the estrous cycle this monoamine exerts the opposite action on LH secretion (the morning time of diestrus 1 and diestrus 2 stages), testifying to the modulating serotonin role in the control of the hypophyseal gonadotropic function. In experiments on ovariectomized female rats, some of which were given estradiol benzoate, it was shown that serotonin injection into PR was accompanied by a decrease in the blood LH level only in ovariectomized rats, treated with estradiol, and did not change LH secretion in sterilized female rats.