[Effect of parathormone on bone blood flow in rats--possible role of NO]. / Ucinek parathormonu na prutok krve kostmi potkanu--mozná úcast NO.

UNLABELLED: Parathyroid hormone (PTH)--besides its main osteotrophic action--exerts also vascular effect demonstrated formerly also in bones. The aim of the presented work was to verify this effect of PTH using the radioactive microsphere method and to ascertain simultaneously whether NO does participate or not in this effect of PTH. We performed two experiments which were arranged in the same way, as follows: group I--controls, group II--PTH, group III--L-NAME, group IV--L-NAME + PTH. Parathyroid hormone 1.34 fragment (Sigma, USA) was administered to each animal 6-12 minutes before the injection of radioactive microspheres in the dose of 3 micrograms in the experiment A, 10 micrograms in the experiment B. NG-nitro-L-arginin methyl ester (Sigma, USA) was given in the food for ten days before the experiment in the concentration of 0.025% in experiment A, 0.05% in experiment B. RESULTS: We present the results of experiment A in the part "Results" of the paper briefly in percentages--they are similar to the results of experiment B, but without statistical significance. Administration of PTH increased statistically significantly the microsphere uptake in tibia and distal femur and also the blood flow in both bones, increased the cardiac output and lowered blood pressure. Administration of L-NAME alone induced decrease of the heart rate only. After the injection of PTH to the rats fed L-NAME there was--compared to the injection of PTH only--the blood flow through both bones significantly lower. The observed increase in the bone blood flow as well as changes in the general circulation show that i.v. injection of PTH under the experimental conditions used does induce vasodilatation in female rats. Influence of these changes by the administration of L-NAME indicates possible participation of the nitric oxide (NO) in the observed effect of PTH on the vessles.

[Role of IGF-I and NO on regulation of regional blood circulation in the bones of rats]. / Príspevek k úloze IGF-I a NO v regulacích místního krevního obehu v kostech potkaních samic.

UNLABELLED: We present the results of two experiments aimed at the role of IGF-I and NO in the regulation of bone blood flow. In the first experiment A we determined the blood circulation in tibia and distal part of femur and the blood level of IGF-I after oophorectomy (OOX, 4 weeks before the experiment) and/or administration of NG-nitro-L-arginin methyl ester (L-NAME, Sigma, USA, 0.05% in the food for 10 days before the experiment). In the second experiment B we checked up the possibility of correlation between the bone blood flow and IGF-I level in female rats control and after the administration of estradiol (Agofollin Depot, Biotika, Slovak Republic, 1 mg s.c., two times weekly, for 4 weeks before the experiment). The bone blood flow was ascertained by means of 85-Sr microsphere (NEN, USA) technique, IGF level was estimated with Rat IGF-I RIA kit (DSL, USA). RESULTS: Experiment A: group I: controls--sham operation, group II: oophorectomy (OOX), group III: L-NAME + sham operation, group IV: OOX + L-NAME. OOX elevated the 85-Sr microsphere uptake and bone blood flow in tibia and distal femur. The administration of L-NAME to non-castrated females lowered significantly the blood flow in the femur only, whereas in OOX females it inhibited completely the usual OOX-induced increase in circulatory indicators in both bones. IGF-I level was higher after OOX, administration of L-NAME did not exert any effect on it. Experiment B: group I: control females, group II: estradiol. After the administration of estradiol, there was marked decrease in the uptake of 85-Sr microspheres and blood flow in both bones, decrease in body weight, cardiac output, heart rate, blood pressure and also in the blood level of IGF-I. Density and ash weight of the tibia were elevated. Important results found in the group I of experiment B seem to be the correlations between the blood level of IGF-I and 85-Sr microsphere uptake in tibia (r = 0.68, p < 0.01), between IGF-I and blood flow in tibia (r = 0.54, p < 0.05) and between IGF-I and 85-Sr microsphere uptake in distal femur (r = 0.55, p < 0.05). However, in the group II of females after estradiol no significant dependence could be demonstrated. The results support the conception of the role of IGF-I and NO in the regulation of local blood flow also in the bones of rats. The possible sequence of the interrelations could be as follows: OOX--increase in the blood level of IGF-I--increase in the production of NO--vasodilatation and increase in the bone blood flow. Significant correlations between the blood level of IGF-I and bone blood flow represent further evidence of the participation of IGF-I in the regulation of bone blood flow in rats.

[Effect of calcitonin on regional blood flow in bones, serum levels of IGF-I and osteocalcin, density and weight of bone ash in oophorectomized rats]. / Vliv kalcitoninu na místní krevní obeh v kostech, hladinu IGF-I a osteokalcinu v krvi, hustotu a hmotnost popela kosti u ooforektomovaných potkaních samic.

It is known that in cases of increased bone remodelation rate, i.e. after castration, local bone blood flow is also increased. But in case of adequate hormonal substitution, bone blood flow, similarly as the remodelation rate, return to normal ranges. Until now, there is no knowledge, if other drug can influence enhanced bone blood flow in oophorectomized animals. In this study authors treated oophorectomized female rats with calcitonin and followed bone blood flow, together with biochemical parameters of bone remodelation activity (osteocalcine), IGF-I levels, weight of bone ash and bone density. The female rats were divided in four groups: controls, oophorectomized, with calcitonin and oophorectomized with calcitonin. The bone blood flow was determined by method of body dispersion of radioactive strontium labelled microspheres. The results of this study show, that, in comparison with controls, the bone remodelation rate (documented with increased osteocalcine levels) and radioactive strontium labelled microspheres capture in bone in increased after oophorectomy (p < 0.05). Ash weight and bone density were decreased (p < 0.05). Simultaneously, the blood IGF-I levels were increased (p < 0.05). After oophorectomized animals were treated with calcitonin, all parameters mentioned above headed towards normal ranges in comparison with group of oophorectomized female rats without calcitonin (p < 0.05). Changes of serum IGF-I levels follow changes of microspheres capture in each group of animals. Authors support the hypothesis, that blood levels of IGF-I could influence local bone blood flow. Calcitonin treatment of oophorectomized animals diminishes also decrement of ash weight and bone density. Results of this work show, that similarly as hormonal substitution therapy after oophorectomy, calcitonin also diminishes increased bone blood flow and bone remodelation parameters. The degree of bone blood flow is probably connected with activity of bone remodelling.

[Is there a relation between weight in rats, bone density, ash weight and histomorphometric indicators of trabecular volume and thickness in the bones of extremities?]. / Existuje vztah mezi hmotností potkanu, kostní hustotou, hmotností popela a histomorfometrickými ukazateli trabekulárního objemu a trabekulární sírky v kostech koncetin?

Authors deal with question, if there is possibility to infer bone histological structure (described by histomorphometric parameters of trabecular bone volume and trabecular thickness) from bone density, ash weight or even from weight of animal (rat). Both tibias of each of 30 intact male rats, 90 days old, were processed. Left tibia was utilized to the determination of histomorphometric parameters of undecalcified bone tissue patterns by automatic image analysis. Right tibia was used to the determination of values of bone density, using Archimedes' principle. Values of bone density, ash weight, ash weight related to bone volume and animal weight were correlated with histomorphometric parameters (trabecular bone volume, trabecular thickness) by Pearson's correlation test. One could presume the existence of relation between data, describing bone mass at the histological level (trabecular bone of tibia) and other data, describing mass of whole bone or even animal mass (weight). But no statistically significant correlation was found. The reason of the present results could be in the deviations of trabecular density in marrow of tibia. Because of higher trabecular bone density in metaphyseal and epiphyseal regions, the histomorphometric analysis of trabecular bone is preferentially done in these areas. It is possible, that this irregularity of trabecular tibial density could be the source of the deviations, which could influence the results of correlations determined. The values of bone density, ash weight and animal weight do not influence trabecular bone volume and vice versa: static histomorphometric parameters of trabecular bone do not reflect bone density, ash weight and weight of animal.

[Effect of pamidronate on bone blood flow and serum levels of IGF-I in sham-operated and oophorectomized female rats]. / Ucinek pamidronátu na krevní obeh v kostech a na hladinu IGF-I v krvi potkaních samic náznakove operovaných a ooforektomovaných.

In our previous work [7] we demonstrated that the bisphosphonate pamidronate lowered the bone blood flow of non-castrated female rats and inhibited the increase in bone blood flow after oophorectomy (OOX). In this paper we present the results of two similar experiments but also with the estimation of IGF-I in blood. The blood flow in the bones of female rats was estimated by means of 85-Sr microsphere technique (NEN, USA), the blood level of IGF-I was ascertained with Rat IGF-I RIA Kit (DSL, USA). Both experiments A and B were performed on female rats according to the same experimental scheme: group I--sham-operated controls, group II--OOX (four weeks before the experiment), group III--pamidronate (Aredia, CIBA-Giegy, 0.6 mg i.p. three days in the week, for four weeks), group IV--OOX + pamidronate. The results of both experiments can be summarized as follows:--it was confirmed again that OOX rises the circulatory indicators in the bones as well as the blood level of IGF-I;--pamidronate suppresses the increase in bone blood flow after OOX;--pamidronate does not unequivocally influence the level of IGF-I in blood. Thus, it is very probable that IGF-I plays a role in the increase of bone blood flow after OOX. However, it is still not clear how the deficiency of estrogens influences the blood level of IGF-I. The mode of action of pamidronate on the bone blood flow--mainly elevated after OOX--is not clear as well.

Effect of growth hormone and pamidronate on bone blood flow, bone mineral and IGF-I levels in the rat.

So far it is not known whether the growth hormone (GH) has an effect on the local blood circulation in bones. Using male rats we studied the local blood circulation in the tibia and the distal end of the femur (by means of the uptake of 85Sr-microspheres), the density and ash weight of the tibia, the urinary excretion of pyridinoline (PD) and deoxypyridinoline (DPD) as an indicator of bone resorption and the blood levels of IGF-I after the administration of human GH (4 mg/kg s.c. daily for 4 weeks) and/or bisphosphonate pamidronate (Aredia, CIBA-Geigy, administered in the dose of 3 mg/kg i.p. on day 1, 2, 9 and 10). The rats were divided into four groups: 1. controls, 2. GH, 3. pamidronate, 4. GH plus pamidronate. After the administration of GH, we observed a significant increase in bone blood flow (and in the uptake of 85Sr-microspheres), a decrease in the density and ash weight of the tibia and increased urinary excretion of PD and DPD; IGF-I levels in the blood were non-significantly elevated. Simultaneously administered pamidronate inhibited all significant effects of GH and it also decreased the IGF-I levels in rats treated with GH. After the administration of pamidronate itself the bone density and ash weight of the tibia were increased and urinary DPD excretion was decreased. In view of the known vascular effects of IGF-I, we assume that the increase in bone blood flow after the administration of GH and its reduction after simultaneous administration of pamidronate could be mediated by the changes of IGF-I blood levels, although the effect of pamidronate on IGF-I is still not clear. Regarding the role of blood circulation in rat bones, we consider that our present results are further evidence for the relationship between the blood circulation in bones and bone resorption, although these results do not show how active is bone blood circulation in the regulation of bone tissue metabolism.

[Effect of growth hormone on the structure of bone spongiosa in rats]. / Vliv rustového hormonu na strukturu spongiózní kosti u potkanu.

Changes in bone spongiosa, which follow after administration of growth hormone (GH) are described differently. Histomorphometrically processed value of bone trabecular volume is found higher or lower than normal. In this study, changes of rat bone spongiosa after administration of GH or bisphosphonate pamidronate were followed. The authors found statistically significant widening of histomorphometric parameter of trabecular thickness, but histomorphometrically assessed values of trabecular bone volume were not statistically different from normal rat bones. The structure of spongiosa is changed, the density of trabecular bone is diminished. The hypothesis of trabecular bone increase after GH administration together with resorption blocking agent (pamidronate) was not confirmed. GH causes widening of bone trabeculae. Pamidronate has no influence on bone histomorphometry in this case.

[Effect of growth hormone and other hormones on trabecular bone structure in acromegaly]. / Vliv rustového a nekterých dalsích hormonu na strukturu trámcité kosti akromegaliku.

The influence of growth hormone upon trabecular bone remodelation is not definitely clear. The authors of this study compared static and dynamic histomorphometric data of bone patterns of 28 numbered group of acromegalics and 35 numbered group of healthy individuals. They correlated also levels of growth hormone, thyroxine, prolactin and testosterone in men with histomorphometric parameters in acromegalic patients. The results showed statistically significant differences between normal and acromegalic trabecular bone, which has comparable trabecular volume, but significantly wider bone trabeculae and lower mean trabecular density. There were no correlations found between growth hormone levels and levels of thyroxine, prolactin, measured testosterone and histomorphometric parameters.

[Duration of the effect of growth hormone on spongious bone]. / Pretrvávání vlivu rustového hormonu na kostní spongiózu--pooperacní situace.

The influence of duration of growth hormone action (length of history of acromegaly) upon acromegalic trabecular bone histology was followed in 28 biopted active acromegalics. The histology of trabecular bone was standardized by histomorphometric parameters. No statistically significant relation between length of acromegalic history and any of measured histomorphometric parameters (trabecular volume, trabecular thickness, absolute osteoid volume and osteoid surface) was found. The reason of this finding is probably consequence of serum growth hormone level, which changes during period of history in each acromegalic patient. With aim to find out if growth hormone influences bone histomorphometry of acromegalics after causal treatment (removal of hypophyseal adenoma causing overproduction of growth hormone), the comparison of histomorphometry from bone bioptic patterns of six active acromegalics with their bone patterns average 9.3 years after hypophyseal operation was done. With the exception of one eugonadal woman, all acromegalics were hypogonadal in time of second biopsy. Nevertheless no statistically significant differences between histomorphometric data (trabecular volume, trabecular thickness, surface and absolute volume of osteoid) were found. With knowledge of fact that there is low number of rebiopted acromegalics, these results could support idea of protective action of growth hormone upon trabecular bone of acromegalics during nine years after treatment.

Effect of pamidronate on bone blood flow in oophorectomized rats.

In connection with the known inhibitive action of bisphosphonates on bone resorption we were interested in their possible influence on bone blood flow (BBF). We determined BBF (85Sr-microsphere uptake in the tibia, distal femur and diaphysis of femur), cardiac output, density and ash weight of the tibia, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. Pamidronate (Aredia, CIBA-Geigy, Switzerland) was administered to sham-operated or oophorectomized (OOX) female rats in doses of 0.6 mg i.p. 2 days a week for 4 weeks. 85Sr-microsphere uptake was increased after OOX in the tibia and distal femur, simultaneous pamidronate administration significantly suppressed this increase below the control level. In addition, pamidronate inhibited the 24-h incorporation of 45Ca and 3H-proline in sham-operated females and suppressed the incorporation of 3H-proline that was increased after OOX. Bone density and ash weight were significantly increased after pamidronate administration in both sham-operated and OOX rats. The results of both experiments showing a significant effect of pamidronate on BBF and incorporation of 45Ca and 3H-proline require further verification and elucidation.

[Relation between local blood flow and bone mineralization indicators in the tibia of female rats]. / Vztah mezi místním krevním obehem a ukazateli obsahu minerálu v tibii potkaních samic.

The results presented contribute to the still unclarified question of the role of bone blood flow in the metabolism and mineralization of the bone tissue. We investigated correlation relationships between 85Sr-microsphere uptake (in % dose per g) or local blood flow (in ml/min per g) and density or ash weight (in g per ml of bone tissue) in the tibia of female rats. In four experiments a total of 16 correlations was computed. The following relationships were found statistically significant (p < 0.05): in exp. A (20 intact females): microsphere uptake--ash weight, blood flow--density, blood flow--ash weight, in exp. B (oophorectomy 4 weeks before the experiment, 28 rats): microsphere uptake--ash weight, blood flow--density, blood flow--ash weight, in exp. C (estradiol benzoate 1 mg s.c. twice a week for 4 weeks, 40 rats): microsphere uptake--density, microsphere uptake--ash weight, blood flow--density, in exp. D (20 oophorectomized females on estradiol): microsphere uptake--ash weight, blood flow--ash weight. The results support the hypothesis of an interconnection between the mineralization of bone tissue and local bone blood flow.

[DHEA: another hormonal modulator of bone blood flow in rats]. / DHEA: dalsí hormonální modulátor krevního obehu v kostech potkanu.

Dehydroepiandrosterone (DHEA) is a steroid with important effects on the bone tissue. We tried to check up if it influenced also the bone blood flow (similarly as estradiol and testosterone). We administered DHEA (Sigma) dissolved in dimethylsulphoxide s.c. three times weekly for four weeks in the doses of 15-20 mg per rat on 125 mg/kg body weight to female rats--sham-operated or oophorectomized (OOX). In two experiments (A and B) we ascertained the uptake of 85Sr-microspheres, local blood flow, cardiac output, density and ash weight of the burned tibia, in the third experiment (C) 24 hour incorporation of 45Ca and 3H-proline into the bone. The 85Sr-microsphere uptake in the tibia was elevated after OOX in both experiments A and B; this increase was inhibited completely (and statistically significantly versus the OOX group) by the administration of DHEA. Similar and also significant reactions were found in the microsphere uptake values in the distal end of femur. No significant changes could be demonstrated in the diaphysis of femur and calvaria as well as in the cardiac output, output, blood pressure and heart rate. The incorporation of 45Ca and 3H-proline into the tibia (experiment C) was significantly increased after OOX. The administration of DHEA inhibited this increase significantly in the values of 3H-proline. The density of tibia in both experiments A and B and ash weight of tibia in experiment A, suppressed after OOX, were significantly increased after the administration of DHEA to OOX females. The results show that also DHEA--in the experimental conditions used--has similar effect on the bone blood flow as estradiol and testosterone.

Possible participation of EDRF-NO in the hormonal regulation of bone blood flow in rats.

An increase in bone blood flow (BBF) was observed in rats after castration whereas a decrease in BBF occurred after oestradiol or testosterone. The possible participation of prostaglandins in these changes was demonstrated. The present results show that the endothelium-derived relaxing factor, i. e. nitric oxide (EDRF-NO), might play a role in these hormonal actions on BBF. Until now, almost nothing is known about the possible action of NO on bone circulation. Methylene blue (MB) as a substance blocking EDRF-NO was administered to sham-operated or oophorectomized (OOX) female rats. We determined local blood flow (85Sr-microsphere uptake), cardiac output, blood pressure, heart rate, density of the tibia and ash weight, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. The administration of MB (0.5% in the food for 4 weeks) significantly lowered both 85Sr-microsphere uptake and blood flow values in the tibia and distal femur of sham-operated and OOX rats. MB lowered cardiac output and blood pressure to the same extent, indicating no change in the vascular resistance. After the administration of MB (0.1% in the food), 85Sr-microsphere uptake decreased significantly in the tibia of OOX females while no significant change was found in soft tissues. Bone density and ash weight were significantly lower in OOX rats and in sham-operated rats after MB treatment. Finally, the 24-h incorporation of both 45Ca and 3H-proline decreased significantly in OOX females after MB administration (0.04% in the food). It can be concluded that 1) MB lowers BBF, suggesting the participation of EDRF-NO in BBF regulation, 2) MB does not influence or may even suppress cardiac output and blood pressure in high dosage, 3) MB lowers 24-hour incorporation of 45Ca and 3H-proline into the tibia of OOX rats, which is in agreement with the circulatory effect, 4) MB lowers bone density and ash weight of the tibia in non-castrated female rats. The effects of MB observed in our experiments partially differ from those of arginine-derived blocking agents. This requires further elucidation.

[Further evidence of the role of prostaglandin on the effects of hormones on blood circulation in bones]. / Dalsí doklady o zprostredkování hormonálních úcinku na kostní krevní obeh prostaglandinem.

In a short communication we demonstrated the inhibitory affect of acetylosalicylic acid (ASA) on the increased bone blood flow and 45Ca and 3H-proline incorporation in oophorectomized (OOX) female rats. This finding suggested probable participation of prostaglandin. The aim of the present work was to confirm and extend the initial observation and to find out, whether the administration of ASA did not affect also the decrease in the bone blood flow after the administration of estradiol benzoate (EB). Local blood flow was determined by means of the uptake of 85Sr-microspheres. In experiment A (females) the local circulatory values were increased after OOX significantly in tibia and distal femur, insignificantly in diaphysis of the femur and calvaria; this increase after OOX was suppressed by simultaneous administration of ASA completely in tibia, partially (and statistically insignificantly) in distal femur and diaphysis of the femur; no effect of ASA could be demonstrated in the calvaria. The blood flow through the kidneys of OOX female rats was decreased after ASA, while no change occurred in muscle and skin. The bone mineral content was significantly lower in both groups of OOX females. In experiment B (males), we observed an increase in local circulatory values after ORX in tibia, distal femur and diaphysis of the femur and suppression of this increase by the administration of ASA. These changes were not demonstrable in the calvaria and soft tissues studied. In experiment C (females), we found that significant decrease in the local circulatory values in the tibia after 4 weeks of administration of EB was not altered by simultaneous administration of ASA. Experiment D (females) proved again that 24 hour incorporation of 45Ca and 3H-proline was markedly suppressed by the administration of ASA not only in OOX females but also in sham operated control rats. Thus, the present results confirm the inhibitory effect of ASA on the increase in bone blood flow after castration, indicating with high probability participation of prostaglandin (PGE2?) (while no effect of ASA could be demonstrated on the decrease in bone blood flow after EB). The described blood flow changes are induced by local vascular reactions and occur in the bones of both female and male rats. Marked suppression by ASA of 45Ca and 3H-proline incorporation supports the circulatory results and indicates an important interconnection between metabolic processes and local circulation in the bone. We conclude that prostaglandin may be one of the factors regulating bone blood flow.

[The role of EDRF-NO in the regulation of bone blood flow in rats: inhibition with L-NAME]. / Ucast EDRF-NO v regulacích kostního prutoku krve u potkanu: inhibice s L-NAME.

EDRF-NO probably participates-besides the prostaglandins [3, 4]-in local circulatory changes in the bones of female rats with modified level of sex hormones; we could demonstrate it indirectly using methylene blue as a blocking agent [5]. In this paper, we present corresponding results of two experiments with NG-nitro-arginine methyl ester (L-NAME) as a substance blocking the production of endothelium derived relaxing factor, i.e. nitric oxide (EDRF-NO). Circulatory values were estimated by means of 85Sr-microspheres. In experiment A we ascertained whether the duration of L-NAME administration (0.025% in the food) influenced the effect. It could be demonstrated that the effect of one week's, two weeks', or four weeks' administration of L-NAME was the same: 85Sr-microsphere uptake and blood flow throught the tibia of female rats, increased after oophorectomy (OOX, performed four weeks prior to the experiment), was significantly suppressed to the level in sham-operated animals. In the experiment B, L-NAME was administered in the food in concentration of 0.05% for two weeks prior to the experiment. 85Sr-microsphere uptake was decreased significantly after L-NAME in the tibia of sham-operated females, in the tibia and distal femur of OOX animals; no significant changes were found in the diaphysis of femur and in calvaria. Blood flow values were significantly decreased in all bone samples of OOX females and in tibia of sham-operated rats (besides the local reaction also due to the decrease in the cardiac output). In both experiments the cardiac output was decreased and blood pressure elevated after L-NAME. It can be concluded, from the results of both experiments, that the blockade of EDRF-NO production by L-NAME decreases local circulatory values in the bones of female rats-particularly OOX-in a similar way as methylene blue; however, in contrast to methylene blue, L-NAME induces marked increase in the blood pressure and partially decrease in the cardiac output. Thus, as in the case of methylene blue, the effect of L-NAME on the circulation of blood in the rat bones supports the hypothesis of the participation of EDRF-NO in bone blood flow regulations.

Blood flow and mineral content of the tibia of female and male rats: changes following castration and/or administration of estradiol or testosterone.

We studied changes in the local circulation and mineralization of the rat tibia under different experimental conditions. Four experiments were performed on a total of 155 female and male rats: after oophorectomy (OOX) or orchidectomy (ORX), after the administration of estradiol benzoate (EB, Agofollin Depot, 1 mg/rat once a week or 5 mg/kg body weight once every 5 days for 4 weeks), or after the administration of testosterone (T, Agovirin Depot, 25 mg/kg body weight once every 5 days for 4 weeks). We estimated 85Sr-microsphere uptake and blood flow in the tibia, density of the tibia, and ash weight per bone volume unit. The scheme of the experiments was uniform: experiment A--females--controls, OOX, EB, OOX + EB; experiment B--males--controls, ORX, EB, ORX + EB; experiment C--females--controls, OOX, T, OOX + T; experiment D--males--controls, ORX, T, ORX + T. A sham operation was performed on the animals in the uncastrated groups. The results showed that OOX and ORX stimulated the uptake of 85Sr-microspheres and bone blood flow and reduced both bone density and ash weight, whereas T inconstantly and EB constantly reduced 85Sr-microsphere uptake and bone blood flow and increased bone density and ash weight in both sham-operated and castrated animals. The described changes in the bone blood flow and mineral content under the given experimental conditions suggest a relation in the regulations of both processes, a possible association with resorption of bone, and the importance of the circulation of blood in the metabolism of bone tissue.

Inhibitory effect of hydrocortisone on the blood flow and 45Ca and 3H-proline incorporation into bones of female rats.

We studied the effects of hydrocortisone as a possible regulatory factor of bone blood flow and metabolism. Local bone blood flow in the tibia, distal femur, lumbar vertebra and some soft tissues (using 85Sr-microspheres), as well as 45Ca and 3H-proline incorporation into the tibia, bone density and ash weight per ml of the tibia were measured in sham-operated and oophorectomized female rats in which the influence of hydrocortisone administration (0.004% diet for 5 weeks) was followed. Hydrocortisone markedly lowered 85Sr-microsphere uptake and blood flow through the bones of non-castrated female rats as well as elevated circulatory values in oophorectomized rats. The changes were nearly identical in the three bone samples measured; among the soft tissues only the kidneys showed a less pronounced decrease. Circulatory changes in the bones seem to be caused by local vascular reactions. Hydrocortisone also lowered the 24-hour incorporation of 45Ca and 3H-proline into the tibia of both non-castrated and oophorectomized females. In the tibia of oophorectomized rats, hydrocortisone normalized the decreased bone density and ash weight. The adrenocortical hormones are known to block eicosanoid synthesis by the inhibition of arachidonic acid production. It is possible, therefore, that local circulatory changes in the bones of rats, induced by hydrocortisone, are mediated by the changes in prostaglandin production.

[A decrease in blood flow and incorporation of 45Ca and 3H-proline in the bones in pregnant female rats]. / Snízení prutoku krve a inkorporace 45Ca a 3H-prolinu v kostech brezích potkaních samic.

In the experiments on rats, the bone blood flow may be influenced by the deficiency as well by the administration of sex hormones. The aim of this work was to investigate the bone circulation (determined by means of 85Sr-microspheres, experiment A and B) and the incorporation of 45Ca and 3H-proline into the tibia (experiment C) in the last stage of pregnancy (from 18 to 21 days), i.e. in the physiological condition with elevated level of estrogens. In the experiment A and B, the uptake of 85Sr-microspheres and blood flow in pregnant rats was lower in the tibia and distal femur, the blood flow only was significantly lower also in the humerus and the calvaria. In kidneys, liver, muscle and skin, there was no difference in microsphere uptake; the blood flow was in pregnant females lower only in the kidneys. In perirenal fat, the microsphere uptake and blood flow was several times higher in pregnant rats than in controls. 24 hour incorporation of 45Ca and 3H-proline was in pregnant females significantly lower. The bone density and ash weight was higher in pregnant rats in experiment A. Estradiol concentration in plasma was in experiment B in pregnant rats significantly higher (by 24.8%). Thus, in pregnant female rats, we found lower bone blood flow and lower incorporation of 45Ca and 3H-proline along with normal or higher bone mineral content in the condition, where enhanced resorption and formation of the bone had been described. The changes in bone blood flow and possible role of estrogens in this situation remain to be elucidated.

[Radionuclides in endocrinology diagnosis and experimental research]. / Radionuklidy v endokrinologické diagnostice a experimentálním výzkumu.

In the article, a brief historical survey is presented of the utilization of radioactive isotopes in endocrinology and, in particular, in the 3rd Medical Clinic and Laboratory for endocrinology and metabolism. In the following, the results of our own work on the local circulation of blood in rats, its regulations and changes, are presented, i.e.: blood flow through the thyroid gland, adrenals and pituitary, local and general circulatory effects of thyroid hormones and, particularly, local blood flow through the bones in rats-changes after castration and administration of sex hormones in both females and males, possible mechanisms of the changes and functional interconnections with regard to the possible participation of the flow changes in the pathogenesis of osteopathies.

Relationships between local circulatory changes in the tibia and kidney of male and female rats after castration and administration of estradiol or testosterone.

The effects of castration and of the four weeks' administration of estradiol or testosterone on the blood circulation in the tibia and the kidney (expressed as the 85Sr-microsphere uptake values, which are not influenced by simultaneous changes in cardiac output) were studied in four experiments on a total of 147 rats (68 females, 79 males), relative weights being noted at the same time. 85Sr-microsphere uptake in the tibia rose markedly after castration in both males and females, fell after estradiol benzoate in intact females and intact and orchidectomized males and also fell after testosterone in intact and oophorectomized females and orchidectomized males. 85Sr-microsphere uptake in the kidney rose after castration only in males in experiments B; it fell after estradiol in orchidectomized males and fell after testosterone in intact females and males and in orchidectomized males. Relative tibial weight fell in castrated females, but in castrated males only in experiment D; after estradiol it rose only in males (intact and orchidectomized) and rose after testosterone in intact and oophorectomized females and orchidectomized males. Relative kidney weight fell after castration in both males and females, rose after estradiol in intact females and intact and orchidectomized males and rose after testosterone in intact and castrated males and females. In all four experiments there was a demonstrable statistically significant correlation between the 85Sr-microsphere uptake values in the tibia and the kidney. The relative weights displayed a similar correlation.(ABSTRACT TRUNCATED AT 250 WORDS)