Influence of magnesium on the beta-inhibition of catecholamines in the uterine circular muscle of estrogen-treated rats

The effects of Mg and isoprenaline on the uterine circular muscle of ovariectomized rats which were injected with estradiol for 2--6 days were investigated. The muscle strip exhibited an action potential that was composed of a spike and a plateau, and also exhibited a twitch-like contraction due to electrical stimulation. The duration of the action potential became longer when the treatment with estrogen was applied until the maximal effect was built up in 4--5 days. Both the duration of the action potential and the amplitude of contraction were reduced when isoprenaline was applied. When Mg (0.5 mM) was added to the bathing solution these beta-effects were progressively potentiated and the maximal effect was obtained in about 1 hr. An increase in membrane conductance was induced by the application of isoprenaline in a control Locke solution and it was further accelerated by exposure to Mg-containing solution. The possibility that the beta-action is potentiated by Mg ions which penetrated into the membrane is concluded.     

Effect of ketotifen on the distribution and degranulation of uterine eosinophils in estrogen-treated rats

Eosinophil leukocytes migrate from the blood to the uterus under estrogen stimulation, redistribute through uterine extravascular compartment, degranulate in the organ, and release agents that are involved in several parameters of estrogen action. Agents that induce blood eosinopenia, block their migration to the uterus, interfere with their redistribution within the organ or modify their degranulation, selectively interfere with eosinophil-mediated responses to estrogen. The present study investigated whether ketotifen, an antiallergic agent that inhibits allergen-induced eosinophil degranulation, interferes with estrogen-induced eosinophil migration to the uterus and their subsequent degranulation. Ketotifen does not interfere with estrogen-induced eosinophil accumulation in the uterus, but decreases the proportion of eosinophils located in endometrium and inhibitis their degranulation. These results suggest that neither histamine, calcium or slow reacting substance of anaphilaxis are involved in eosinophil migration to the uterus. The inhibition by ketotifen of eosinophil degranulation may diminish eosinophil migration through extravascular compartment via a decrease in the release from degranulating eosinophils of enzymes required for this migration. It is possible that the inhibition by ketotifen of both, eosinophil degranulation and eosinophil motility through uterine extravascular compartment, interfere with eosinophil-mediated responses to estrogen or with other functions of these cells.     

Skeletal effects of magnesium deficiency in normal,ovariectomized, and estrogen-treated rats

The effects of magnesium deficiency in ovariectomized and estrogen-treated rats were examined in histological sections of bones and various soft tissues. The changes observed in the femora of intact rats deprived of magnesium for three weeks were: 1. a general increase in diaphyseal thickness, 2. the presence of localized fibrous or bony-like masses in subperiosteal and metaphyseal sites, and 3. the occurrence, although rare, of endosteal hyperplasia. In ovariectomized, magnesium-deprived animals, the incidence and location of fibrous masses were similar to that in the femora of magnesium-deficient intact rats; however, no increase in diaphyseal thickness was noted. Daily injections of 25 μg estradiol caused a reduction of the frequency of skeletal hyperplasia from 80% to 20%, as well as a reduction in femoral diaphyseal thickness. Estradiol hormone administration also brought about a marked alleviation of the dermal and neural manifestations of magnesium deficiency, but, at the same time, caused an exacerbation of renal calcinosis.     

Skeletal effects of magnesium deficiency in normal, ovariectomized, and estrogen-treated rats.

The effects of magnesium deficiency in ovariectomized and estrogen-treated rats were examined in histological sections of bones and various soft tissues. The changes observed in the femora of intact rats deprived of magnesium for three weeks were: 1. a general increase in diaphyseal thickness, 2. the presence of localized fibrous or bony-like masses in subperiosteal and metaphyseal sites, and 3. the occurrence, although rare, of endosteal hyperplasia. In ovariectomized, magniesium-deprived animals, the incidence and location of fibrous masses were similar to that in the femora of magnesium-deficient intact rats; however, no increase in diaphyseal thickness was noted. Daily injections of 25 mug estradiol caused a reduction of the frequency of skeletal hyperplasia from 80% to 20%, as well as a reduction in femoral diaphyseal thickness. Estradiol hormone administration also brought about a marked alleviation of the dermal and neural manifestations of magnesium deficiency, but, at the same time, caused an exacerbation of renal calcinosis.     

Comparative uterine effects on ovariectomized rats after repeated treatment with different vaginal estrogen formulations

Objective

Topical estrogen therapy is recommended for the treatment of vaginal atrophy. This study was designed to compare the uterotrophic effects of a new estrogen vaginal formulation (0.005% estriol vaginal gel) and other existing topical treatments (Ovestinon^® and Colpotrofin^®).

Methods

Each one of the studied formulations was administered intravaginally to groups of ovariectomized rats with cytologically confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14 days, the animals were sacrificed and their vaginas and uteri removed. All uteri were weighted. Uteri and vaginas were fixed for histological evaluation.

Results

All three active formulations proved to be very effective in the cytological reversal of vaginal atrophy. However, they differ in their effects in the uteri. Ovestinon^® and Colpotrofin^® produced a significant increase in uterine weight, myometrial and endometrial thickness as well as histological modifications in the endometrium suggestive of estrogenic activity. Conversely, animals treated with 0.005% estriol vaginal gel, did not show significant weight increase or any other macroscopical or microcospical modifications of the uteri, an effect comparable to placebo.

Conclusions

There are significant differences in the uterotrophic effect of three different topical estrogen formulations as tested in a rat model of vaginal postmenopausal atrophy. While the three formulations were equally effective in reversing vaginal atrophy, only the newly developed ultra-low dose 0.005% estriol vaginal gel has proved to lack any significant estrogenic effect on the uterus.     

Comparative effects of hindlimb suspension and exercise on skeletal muscle myosin isozymes in rats

Summary The purpose of this study was to ascertain the time course of changes, whilst suspending the hindlimb and physical exercise training, of myosin light chain (LC) isoform expression in rat soleus and vastus lateralis muscles. Two groups of six rats were suspended by their tails for 1 or 2 weeks, two other groups of ten rats each were subjected to exercise training on a treadmill for 9 weeks, one to an endurance training programme (1-h running at 20 m · min^–1 5 days · week^–1), and the other to a sprint programme (30-s bouts of running at 60 m · min^–1 with rest periods of 5 min). At the end of these experimental procedures, soleus and vastus lateralis superficialis muscles were removed for myosin LC isoform determination by two-dimensional gel electrophoresis. Hindlimb suspension for 2 weeks significantly increased the proportion of fast myosin LC and decreased slow myosin LC expression in the soleus muscle. The pattern of myosin LC was unchanged in the vastus lateralis muscle. Sprint training or endurance training for 9 weeks increased the percentage of slow myosin LC in vastus lateralis muscle, whereas soleus muscle myosin LC was not modified. These data indicate that hindlimb suspension influences myosin LC expression in postural muscle, whereas physical training acts essentially on phasic muscle. There were no differences in myosin LC observed under the influence of sprint- or endurance-training programme.     

Studies on the renal pigment of estrogen-treated rats histochemistry and electron microscopy

Although it has been shown that the administration of estrogen to rats is associated with renal pigmentation, neither the nature nor the precise ultrastructural location of the pigment have been yet established.Sequential histochemical and electron microscopic studies carried out in kidneys of Wistar female rats injected intramuscularly with estradiol at various intervals during 7 months, indicated that the pigment accumulating in the epithelium of proximal convoluted tubules fundamentally consisted of hemosiderin, although some other constituents appear to be also present. The pigment deposits were located within lysosomes that with time became post-lysosomes. These deposits differ from those of lipofuscin or ceroid pigments. The possible functional implications of this estrogenassociated hemosiderin pigment remain unknown.     

Effects of sexual steroid hormones treatment on Ca2+ sensitivity of chemically skinned uterine muscle fibers from ovariectomized rats

We considered the possible relationship between the serum levels of progesterone and estradiol-17 beta, which were controlled to that of several stages in normal pregnant rats, and the Ca2+ sensitivity, defined as the pCa required for half maximum activation of force production, of chemically skinned uterine muscle fibers from ovariectomized rats. The Ca2+ sensitivity was negligibly influenced by the levels of these hormones.     

Effect of swimming to exhaustion, at low temperatures, on serum Zn, Cu, Mg and Ca in rats

In order to study the response of plasma trace minerals during exercise in cold water at varying temperatures, three groups of ten male Wistar rats each were forced to swim until exhaustion in water at different constant temperatures (10, 20 and 32 degrees C), while another 3 groups were kept at rest in water at the same temperatures and another group at rest out of the water, at room temperature (21 degrees C). Rectal temperature (RT) was measured before and after the exercise. Samples of arterial blood were obtained under anaesthesia (pentobarbital) from the abdominal aorta after the exercise, and serum concentrations of Cu, Zn, Mg and Ca were determined by flame atomic absorption spectrophotometry (FAAS). The swimming time (ST) decreased in cold water, the values obtained at 10 and 20 degrees C being 3.3% and 8.5%, respectively, of those observed at 32 degrees C. The RT of the animals swimming at 32 degrees C was 32.5 +/- 1.8 degrees C (mean +/- SD) and fell to 25.0 +/- 2.0 and to 19.1 +/- 1.5 degrees C in those swimming, respectively, at 20 and 10 degrees C. The concentrations of Mg, Cu and Ca were significantly higher (+50%, +36% and +7%, respectively) in animals subjected to exercise with respect to the control groups in water, although there were no differences among the three groups. On the contrary, Zn rose progressively with the increase of WT (+32% at 10 degrees C, +60% at 20 degrees C and +76% at 32 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative investigation of the effects of metoprolol, propranolol, practolol, and verapamil in the acute phase of experimental myocardial infarction

Summary Myocardial infarction in rats was produced by ligation of the left coronary artery. To ensure exact comparison of drug effects, the extent of the myocardial zone excluded from the coronary circulation was determined in each animal, and the experimental data were related to it. For this purpose, the hearts were perfused with Evans blue, and after the photometric determination of the dye content of the hearts the percentage of ischemic myocardium was calculated. With metoprolol, propranolol, and verapamil a significant increase of the survival times was obtained (min/% of non-ischemic myocardium). Metoprolol and propranolol also significantly increased the survival rates. None of the-blockers exerted an antiarrhythmic effect. The arrhythmias were prevented by higher doses of the calcium antagonist verapamil which, however, decreased the survival times. All-blocking agents delayed the typical elevation of the ST-segment in the electrocardiogram, and reduced the increase of the activity of the serum creatine kinase. Propranolol and metoprolol antagonized the blood pH decrease obtained after coronary occlusion. Results concerning heart rate, and arterial and central venous pressures are also reported. — The findings with metoprolol, especially, indicate that the essential mechanism in the therapeutic action of-blockers is their ability to block the cardiac ₁-receptors.Supported by the Deutsche Forschungsgemeinschaft     

Effects of Ca2+ on the contractility and Sr2+ accumulation in the quail oviductal smooth muscle

There occur strong spontaneous contractions in the avian oviduct, which are considered to effect the locus of the ovum during ovum transport. Previously it has been shown that stretch regulates these contractions by means of some unknown mechanisms in this tissue. When a transversal strip, cut from the proximal magnum of the oviduct, was first kept at the length (L₀= length in situ) and then stretched to the length 200% L₀ the total integrated area of contractions increased 3.67±0.63 (6) times greater (p<0.01) than the contractility at the length L_o. Ca²⁺ concentration of 5 mM increased the total integrated area of the contractions 1.42±0.22 (7) greater than the control while the increase at 8 mM was only 1.17±0.30 (7). 0.5 mM Ca²⁺ decreased the contractility to 0.72±0.15 (7). In a 50 μM EGTA containing solution, the contractility decreased in a few minutes. Sr²⁺ used as an indirect tracer of Ca²⁺ accumulated both in control and stretched strips in the sarcoplasmic reticulum, the mitochondria, and the sarcolemma. The electron-dense deposits were, however, most clearly seen in the sarcolemma. Compared to the Sr²⁺ accumulating sites in erythrocytes, deposits were on the outer side of the cell membrane, thus suggesting the glycocalyx as an important site for Ca²⁺ exchange in this smooth muscle. The sarcolemmal invaginations, caveolae, accumulated Sr²⁺ similarly to other parts of the sarcolemma. During ovum transport, stretch changes the Ca²⁺ accessibility to muscle cells, and at structural level, this takes place in the sarcolemma.     

Activation of skinned arthropod muscle fibres by Ca2+ and Sr2+

Summary Mechanically skinned skeletal muscle fibres of three crustaceans (barnacle, crayfish and crab) and two insects (cockroach and cricket) were activated in Ca²⁺- and Sr²⁺-buffered solutions of different concentrations and the isometric force response was determined. The maximum force response induced by Sr²⁺ (P ₀ ^Sr ) was only 0–10% of that induced by Ca²⁺ (P ₀ ^Ca ) in all crustacean muscles, but approached 90% in insects. Experiments on barnacle muscle fibres activated simultaneously by Ca²⁺ and Sr²⁺ suggested that Sr²⁺ competes with Ca²⁺ for binding onto the regulatory sites without, however, being able to turn all of them on as efficiently as Ca²⁺. Interestingly, the ratioP ₀ ^Sr /P ₀ ^Ca and the sensitivity for both Sr²⁺ and Ca²⁺ increased substantially after 4–6 h following the dissection of the animals in most intact decapod muscle fibres and after 24 h in most barnacle muscle fibres. The steepness of the activation curves for both Ca²⁺ and Sr²⁺ was similar for each muscle regardless of the age of the fibre and implied that more than 2 Ca²⁺ (2 Sr²⁺) were involved in the activation process of each muscle.A Ca²⁺-induced Ca²⁺ release mechanism of physiological importance was found to operate in all arthropod muscle fibres investigated.     

The effects of Ca2+ and Sr2+ at different modes of activation in the smooth muscle of the rat portal vein

The dependence of Ca2+ for different modes of activation has been investigated in the rat portal vein in vitro by evaluating the effects of substituting Sr2+ for Ca2+ in the extracellular fluid. For the spontaneous contractile activity as well as for contractures induced by depolarizing (high-K+) solution Sr2+ can to a large extent replace Ca2+. Sr2+ is however a poor Ca2+-substitute for the contractile response induced by alpha-stimulation (noradrenaline). The inhibition of spontaneous contractions by beta-stimulation (isoprenaline) is markedly less pronounced in Sr2+ solutions. Available data in the literature suggest that agonist interaction with alpha-receptors, in contrast to beta-receptors, is Ca2+ independent. Our results thus suggest that there exists a Ca2+ specific step between the alpha-receptor agonist occupancy and membrane excitation.