The effects of simultaneous alcohol and cobalt chloride administration on the cardiovascular system of rats.

CFY male rats received drinking water which contained 10% ethyl alcohol and 5% sugar and were treated with 50 mg/kg daily doses of cobalt chloride for three weeks by gavage. Haemodynamic examinations were carried out using radioactive microspheres. Alcohol caused no significant injury of the structure of the myocardium, while cobalt chloride caused incipient multifocal myocytolysis. Blood pressure and nutritive blood flow of the heart were decreased slightly by alcohol and significantly by cobalt chloride. Alcohol additively increased the effect of cobalt chloride decreasing the nutritive blood flow of the heart. It is suggested, that hypoxia increased by dual exposure is responsible for the aggravating effect of alcohol on the myocardial injury caused by the cobalt salt.

Interaction of ACTH, beta-endorphin and alpha-melanocyte stimulating hormone in relation to the corticosteroid production of isolated rat adrenocortical zona fasciculata and zona glomerulosa cells.

The combined effects of ACTH, beta-endorphin (beta-EP) and alpha-MSH were studied on the corticosteroidogenesis of isolated rat adrenocortical zona fasciculata and zona glomerulosa cells. beta-EP potentiated the effects of ACTH and alpha-MSH on the zona fasciculata corticosterone production but inhibited those on the zona glomerulosa aldosterone production. beta-EP did not affect the combined action of 4 x 10(-11) M ACTH and 5 x 10(-9) M alpha-MSH on the zona fasciculata or the zona glomerulosa cells, but it inhibited the stimulatory action of the combination of 1.6 x 10(-10) M ACTH and 10(-9) M alpha-MSH on the zona glomerulosa aldosterone production. An interaction of ACTH, beta-EP and alpha-MSH in relation to the zona fasciculata and zona glomerulosa corticosteroid production was found.

Altered ovarian progesterone secretion induced by cadmium fails to interfere with embryo transport in the oviduct of the rat.

The effect of Cadmium (Cd) on embryo transport through the oviduct and on ovarian progesterone (P) secretion were studied in the rat. Animals were given 2.5, 5, 10 mg/kg CdCl2 or 1.0 mL/kg NaCl sc on day 1 of pregnancy. On days 1, 2, 3, 4, and 5, they were anesthetized with pentobarbital, cannulae were inserted in one of the utero-ovarian veins, and 5-minute blood samples were taken from the ovary. Ovarian venous outflow was recorded, P was determined from the blood fractions, and secretion rates were calculated. P levels were determined in peripheral blood. Body weights and the wet weight of adrenals, ovaries, and oviducts were checked; oviducts and uterine horns were flushed; and number, location, and developmental stage of embryos were observed. Cd content of the oviducts was measured. Cd accumulated dose and time dependently in oviducts and induced a dose-dependent depression and delay in the rise of ovarian P secretion during days 1 through 5 of pregnancy. In the peripheral blood, P levels also failed to rise until day 4 of pregnancy in Cd-treated rats. In embryo transfer, however, no alteration could be observed. It is hypothesized that lack of vascular contact in the oviduct makes it possible for the preimplantation embryos to escape toxic effects of Cd.

Effect of lorglumide (CR-1409) on pancreatic secretory and trophic response to caerulein in newborn rats.

The authors investigated whether lorglumide a specific CCK-receptor antagonist affects the pancreatic actions of caerulein in female newborn Wistar rats. Pancreatic secretory response (expressed as the decrease in specific trypsin activity in the pancreas) was studied in 11-day-old rats following acute administration of saline (control), caerulein (0.3, 1, or 3 micrograms/kg s.c.) either without or with lorglumide (10 mg/kg s.c.). Lorglumide was given 15 min before caerulein. In chronic studies rats were treated 3x/day for 10 days from the day of birth (Day 1) with caerulein and lorglumide as above. On Day 11 the rats were decapitated and exsanguinated, their pancreas removed and analyzed. Acute administration of caerulein induced a dose-dependent depletion of specific trypsin activity from the pancreas and this was antagonized by lorglumide. Chronic treatment with each dose of the peptide increased total pancreatic trypsin content. Besides, the 3 micrograms/kg dose caused to increase pancreatic protein, DNA, and amylase content and to increase plasma corticosterone level. Chronic administration of lorglumide did not influence normal pancreatic growth, while it strongly inhibited the increase in trypsin content evoked by caerulein. However, lorglumide, given alone or in combination with caerulein, induced a significant increase in pancreatic amylase content without affecting plasma corticosterone level.

Differential prostaglandin formation induced by convulsions in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation.

Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D2 and E2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD2 and PGE2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD2 synthesis in DBA2 mice disappeared concomitantly with the age-related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE2 formation persisted. These results suggest that a deficiency of cerebral PGD2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsions, acoustically induced seizures of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy.

Uptake and distribution of Cd in the ovaries, adrenals, and pituitary in pseudopregnant rats: effect of Cd on progesterone serum levels.

Pseudopregnant (PSP) rats were treated with 3.5 or 7.0 mg/kg body wt of CdCl2 on Day 1 of PSP sc. In the lower dose Cd content of the ovaries (luteal and nonluteal tissues), adrenals, pituitary, and blood on Days 1, 2, 5, 8, 10, and 12, and in the higher dose that of luteal and nonluteal tissue on Days 2 and 5 of PSP were determined with atomic absorption spectrophotometry. A rapid incorporation into the corpora lutea was measured on Day 1 and Day 2 of PSP followed by a decrease of Cd content toward the end of PSP whereas the nonluteal tissue, adrenals, and pituitary accumulated Cd gradually until the fifth to 10th day, respectively. Progesterone (P) serum levels were measured with RIA in the blood collected daily from the jugular vein following administration of 3.5 to 7.0 mg/kg body wt of CdCl2 sc on Day 1 or Day 8 of PSP. The serum levels of P remained unchanged when CdCl2 was administered on Day 1 of PSP; however, 7.0 mg/kg body wt CdCl2 given on Day 8 of PSP induced a significant decrease in serum levels of P. It is supposed that the regressing luteal tissue is more sensitive to the toxic effects of Cd than the developing one.

Long-term effects of a single cadmium chloride injection on the ovulation, ovarian progesterone and estradiol-17 beta secretion in rats.

On the day of dioestrus II rats were given 5, 10 or 15 mg/kg of cadmium chloride (CdCl2), or 1, 0 ml/kg of 0.9% NaCl solution. Then ovarian cycle was checked daily for a period of 12 cycle length. On the day of oestrus or expected oestrus in the 13th cycle the animals were anaesthetized with pentobarbital and cannulas were inserted in one of the femoral arteries and veins and in one of the utero-ovarian veins. Five-minute blood fractions were collected for 40 minutes and following the first blood samples 10 IU of hCG were injected iv. Ovarian venous outflow and blood pressure were continuously recorded. From the blood fractions progesterone (P) and oestradiol-17 beta (E2) were determined with RIA and the P and E2 secretion rates of ovary were calculated. Ovaries were excised and oviducts were flushed for counting oocytes. CdCl2 shortly after its administration induced a (dose-dependent) anoestrous period which turned into regular or irregular cycles depending on the dose. Part (28-32%) of the oestrous animals (14% that of the controls) remained unovulatory, when ovulation occurred normal number of ova was found. None of the doses of CdCl2 has influenced the blood pressure of animals and blood flow of the ovary. The basal secretion rate of P and E2 was not changed in the ovary compared to the controls. The hCG induced rise of P secretion, however, in the animals treated with 5 and 10 mg/kg bw CdCl2 was diminished and delayed, while in the animals treated with the 15 mg/kg Cd dose a complete lack of response was observed.

Long-term salt loading impairs pituitary responsiveness to ACTH secretagogues and stress in rats.

Male Wistar rats were allowed to drink tap water ad lib (W), 2% saline (S) or 2% saline containing dexamethasone (S + D, 1 mg/l) for 7 days. On the 8th day rats were subjected to a 3-min ether stress. Plasma ACTH, corticosterone and prolactin concentrations were determined before and after ether exposure. Prestress concentrations of plasma ACTH were low and did not vary among the three groups. In response to ether stress W rats exhibited twice as high plasma ACTH concentrations as did S rats. Rats of the S + D group exhibited a small but statistically significant ACTH response. Plasma corticosterone concentration in S rats was increased while in S + D rats was significantly decreased under resting conditions compared to that in W rats. Ether stress caused large increases in plasma corticosterone concentrations in W and S rats while a small but statistically significant increase was observed in S + D rats. Prolactin responses to ether were smaller in groups S and S + D than in group W. To test whether the decreased ACTH response to ether exposure was a result of a decreased sensitivity of corticotrope cells to corticotropin releasing factor (CRF)-41 or arginine vasopressin (AVP), adenohypophysial fragments from W, S and S + D rats were incubated in the presence of different doses of CRF-41 or AVP. Pituitary fragments obtained from W rats secreted larger amounts of ACTH than did pituitaries from S rats in response to either CRF-41 or AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of acute alcohol intake on certain cardiovascular functions in healthy young males]. / Akut alkoholbevitel hatása egyes cardiovascularis funkciókra fiatal egészséges férfiakon.

.15, 0.25 and 0.5 g/kg alcohol in the form of 40% brandy in one week intervals was consumed by eight healthy, regularly trained young men volunteers. Blood alcohol level, blood pressure and ECG were registered before and 30, 60 and 90 min after, each alcohol consumption. The cardiac output was measured with a radiocirculographic method before and 45 min after alcohol consumption. The cardiac index, stroke volume, stroke index, and total peripheral resistance (TPR) were calculated. With increase of the alcohol dose the blood alcohol level increased, while cardiac output, cardiac index, stroke volume, stroke index, and the systolic blood pressure fell. The other parameters examined--heart rate, diastolic blood pressure, TPR among others--remained unchanged. The ECG was normal. The highest no effect alcohol dose was less than 0.15 g/kg (0.1, k/kg). It is concluded that, depending on the dose, alcohol has practically no effect on the majority of the heart-functions, however, in the range of 0.1 to 0.5 g/kg it has a depressive influence, i.e. lowers the pump-function of the heart and, at 0.5 g/kg the arterial blood pressure.

[The effect of composite filling materials on the diameter of the blood vessels of the dental pulp in rat teeth]. / Kompozíciós tömöanyagok hatása patkányfogak pulpalis ereinek átméröjére.

The authors tested the effect of some of the characteristic types of composite filling materials in a vital-microscope test. The results show that all the four tested filling materials (Biogloss, Evicrol, Isomolar, Isopast) significantly widened the pulpal arteriola; the Biogloss was ineffective for the diameter of the venula, but employing Evicrol, Isomolar and Isopast it was significantly increased. Between the tested materials compared to each difference was observed only during the development of their effect. The hyperaemia observed by us is important in case of short-time inspections as the indicator of acute reactions. Further test is required whether is there any connection between the tested hyperaemia and the toxic effect.

Failure of selective antagonists (CH-38083 and idazoxan) to distinguish between prejunctional and postjunctional alpha 2-adrenoreceptors.

1. The prejunctional alpha 2-adrenoreceptor antagonist activity of CH-38083 (7,8-(methylenedioxi)-14-alpha-hydroxyalloberbane HCl), idazoxan and prazosin was determined against B-HT 920 on the tachycardia induced by cardiac nerve stimulation in pithed rats. Antagonism of cirazoline and B-HT 920 pressor responses was used to assess postjunctional alpha 1- and alpha 2-adrenoreceptor antagonist activities. 2. CH-38083 was more potent than idazoxan in blocking pre- and postjunctional alpha 2-adrenoreceptor sites. There was no difference between the activities of the two selective alpha 2-adrenoreceptor blocking agents on pre- and postjunctional alpha 2-adrenoreceptors. 3. These data classify CH-38083 as a potent and highly selective alpha 2-adrenoreceptor antagonist in vivo and further support evidence of the homogeneity of pre- and postjunctional alpha 2-adrenoreceptors.

Identification of health damage due to alcohol abuse; importance of alterations in cardiac function and blood chemistries.

Like in any other disease, diagnosis of health damage caused by alcohol abuse can be established all the easier and sooner, the more results of medical examinations are taken into consideration simultaneously. Evidence is presented that a larger proportion (96.4%) of alcoholics suffer from compromised cardiac function (the classification function uses 6 variables out of the measured 21 than from disorders of liver function and the metabolism (87.7%) (the classification function uses 12 variables out of the 21). Taking into consideration all the 41 variables (using only 12) the power of discrimination is 99.2% (discriminant analysis).

Inhibition of K+ permeability diminishes alpha 2-adrenoceptor mediated effects on norepinephrine release.

The effect of two different potassium channel blockers, 4-aminopyridine (4-AP) and quinine, on the alpha 2-adrenoceptor mediated modulation of norepinephrine (NE) release was investigated. Pairs of mouse vasa deferentia were loaded with 3H-norepinephrine (3H-NE), superfused continuously, and stimulated electrically. 4-AP (5.3 x 10(-4) M), and quinine (10(-5) M) enhanced the stimulation-evoked release of tritium significantly. The electrically induced release of radioactivity was reduced by alpha 2-adrenoceptor agonists (1-NE and xylazine) and enhanced by the alpha 2-adrenoceptor antagonist yohimbine. Both effects were affected markedly by 4-AP or quinine: the depressant action of 1-NA and xylazine was partially antagonized and the facilitatory effect of yohimbine was completely abolished during the blockade of the potassium channels. It is suggested that the blockade of the potassium permeability counteracts negative feedback modulation; therefore, it seems likely that the stimulation of alpha 2-adrenoceptors leads to an enhanced potassium permeability and hyperpolarization of varicose axon terminals.

Acute effects of low doses of alcohol on the cardiovascular system in young men.

.15, 0.25 and 0.5 g/kg alcohol in the form of 40% brandy in one week intervals was consumed by eight healthy, regularly trained young men volunteers. Blood alcohol level, blood pressure and ECG were registered before and 30, 60 and 90 min after, each alcohol consumption. The cardiac output was measured with a radiocirculographic method before and 45 min after alcohol consumption. The cardiac index, stroke volume, stroke index, and total peripherial resistance (TPR) were calculated. With increase of the alcohol dose the blood alcohol level increased, while cardiac output, cardiac index, stroke volume, stroke index, and the systolic blood pressure fell. The other parameters examined--heart rate, diastolic blood pressure, TPR among others--remained unchanged. The ECG was normal. The highest no effect alcohol dose was less than 0.15 g/kg (approximately 0.1 g/kg). It is concluded that, depending on the dose, alcohol has practically no effect on the majority of the heart-functions, however, in the range of 0.1 to 0.5 g/kg it has a depressive influence, i.e. lowers the pump-function of the heart and, at 0.5 g/kg the arterial blood pressure. Evaluation of the quantitative and qualitative relationships of dose-effect and dose-response of the human heart following acute alcohol consumption needs experiments with various doses in homogeneous groups as well as toxicological investigations in animals.

Structure-activity studies with ACTH/alpha-MSH fragments on corticosteroid secretion of isolated zona glomerulosa and fasciculata cells.

The steroidogenic action of ACTH/alpha-MSH fragments was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(4-7), ACTH-(6-10), ACTH-(4-10) and ACTH-(11-13) stimulated corticosterone production of the zona fasciculata and aldosterone production of the zona glomerulosa cells. ACTH-(7-10) was ineffective. ACTH-(4-7) appeared to be the most potent peptide of the tested fragments. None of the fragments affected the steroidogenic action of ACTH-(1-39). It is suggested that similar to the melanotropic effect of alpha-MSH two 'message' sequences for adrenocortical stimulation exist in the alpha-MSH part of the ACTH molecule.

Study of the luteinizing hormone-induced increase of ovarian blood flow during the estrous cycle in the rat.

CYF rats were anesthetized on various days of the 4-day cycle and blood samples were collected at 5-min interals from the ovarian vein before and after i.v. administration of 5 micrograms/100 g BW of luteinizing hormone (LH). Ovarian venous outflow, blood pressure and hematocrit were continuously recorded, and from the blood samples progesterone (P) and 17 beta-estradiol (E2) were determined by radioimmunoassay (RIA). Ovarian blood flow and P secretion showed a parallel increase on Day 1 (estrus), on Day 2, and on the afternoon of Day 4 (proestrous). LH increased ovarian blood flow each day of the cycle together with P and E2 secretion; however, no relationship was seen between the initial value of hormone secretion and the LH-induced increase of ovarian blood flow. Inhibition of hormone secretion by cycloheximide prevented the LH-induced increase of ovarian blood flow; moreover, a decrease in ovarian blood flow parallel with the diminution of hormone secretion was observed. Indomethacin pretreatment abolished the hyperemic effect of LH and partially inhibited the LH-induced increase of hormone secretion. Propranolol blocked the LH-induced increase of ovarian blood flow and blunted the effect of LH on hormone secretion. It was concluded that in LH-induced hyperemia, cAMP, prostaglandins and other vasoactive metabolites released during the process of hormone synthesis, and also a beta-adrenergic mechanism, are involved in the regulation of ovarian blood flow.