Ganchev, T.

Georgieva, M.

English

Varna Medical University Press: Journals

PLASMA ERYTHROPOIETIN ACTIVITY AND INHIBITORY PROPERTIES A F T E R VARIOUS ADRENERGIC I N F L U E N C E S IN RATS T. Ganchev, M. Georgieva Key-words: erythropoietin — inhibitor of erythropoiesis — adrenergic system The problem of neuro-humoral regulation of erythropoiesis is s t i l l not enough clarified. Erythropoietin (Ep) regulation (a specific factor in maintenance eryth­rocyte homeostasis ( 1 , 11, 13, 15, 18) represents a particular interest. Recently, it has been accepted that another specific factor (an inhibitor of erythropoiesis ( I E ) ) antagonizing E p effect (10, 12, 14, 23, 24) plays also a role in erythropoiesis regulation. I n our previous assays we have found out that beta-adrenoblockade and beta-adrenostimulation reduces E p act iv i ty in rats while Reserpine ( R ) treat­ment doesn't change it significantly (5, 6) . The important role of beta-adreno-receptors in E p act iv i ty regulation has been confirmed, recently, by F i n k and Fisher (1976), too. The purpose of the present study is to examine paralelly plasma E p act ivi ty and I E act iv i ty after adrenergic effects by different mechanism. T h i s would enable us to explain more accurately certain aspects of control function of adre­nergic mediatory unit upon plasma. E p act iv i ty and I E factors which erytrocyte homeostasis is dependent on. Material and methods The observation was carried out on 119 white rats of Wistar bred wi th body weight of 150—200 g. We used Isoprenaline-hydrochloride ( Ip) as a stimulator of beta-adrenoreceptors (twice) in a dose of 5 mg/kg every 10—12 hours (sterile intraperitineal application) and Propranolol (pr) (Obsidan — D D R ) in the same dose and way . A separate group of rats was treated wi th a beta-adrenoblocker and in one hour — with a beta-adrenostimulator in aforementioned doses. We ap­plied Reserpine ( R ) (Rauwasedin — D D R ) in a dose of 2 mg/kg s. с as an inhi­bitor of neuronal l ink of the adrenergic mediatory unit . The controls were trea­ted wi th saline (5). The treatment of rats continued 6 days long. On the 7 t h day their blood was sterilely collected and separated plasma was frozen unt i l use. Plasma E p act iv i ty was estimated on polycytaemic hypoxic mice by 5 9 F e incor­poration into new-formed erythrocytes (modification of Cotes and Bangham's method, 1961). The determination of plasma inhibitory ac t iv i ty has been pre­viously described (6,25). Results and discussion The results from the parallel examination of plasma E p ac t iv i ty are presen­ted on fig. 1 and 2. I n order to explain the mechanism of lowered E p act iv i ty at beta-adrenostimulation and beta-adrenoblockade, we studied plasma inhibi-Plasma erythropoietin activity and. 41 tory properties in this setting. The results received are shown on fig. 3, A , B . ]t can be seen that plasma of rats treated with Ip shows a 7,07 % inhibition s compared to that of E p control (fig. 3a). Plasma of rats treated wi th beta-drenoblocker Pr demonstrates a more considerable inhibition of 15,86 % (fig. 3b). 300 ZOO /00 to Z79.6* 171,5 347p8 Isoprenaline Propr+Lsopr Propranolol ReserpCne Saline Fig . 1. Plasma Ep activity measured by the percentage of 5 9 F e incorporated in the erythro-cytes of polycytemic mice, presentel as a percentage deviation compared to the basal erythro-poiesis accepted as 100 %. *activity level of the control plasma means statistical significance at p<0,025 I n seems that concerning any effects plasma E p ac t iv i ty is increased as c o m pared wi th basal erythropoiesis. The slightest increase is observed with beta-adrenostimulation wi th Ip and the biggest one after inhibition of the neurona-% 30 zo 10 -to 0 w zo 30 40 24,32 1 Isoprenaltne Propr. f Isopn Propranolol ReserpCne i i 5,2. ) 17,04 32,37 Fig . 2. Ep activity in comparison to the control plasma, accepted as 100 %. l ink of the adrenergic mediatory unit wi th R . (fig. 1). I n our opinion, the com-parison of E p act iv i ty after different adrenergic effects wi th that of control plasma is of a greater interest. Plasma shows a tendency to lower levels after beta-adrenostimulation, beta-adrenoblockade and combination of stimulation followed by blockade. E p acti-42 Т. Ganchev, М. Georgieva Incorporation o/ssFe 16 !4 12 10 8 6 4 Z 0 707 % Incorpatlon a/ 53Fe id -14 tz 10 в 6 4 1 0 Ep Standard„C" Z v i t y is greater than that of the control only in animals treated wi th R . (fig. 2) . We tend to explain its lower ac t iv i ty in those treated wi th Ip as compared to the other adrenergic effects by the lower E p production and the presence of I E (fig 3a). i n previous studies we have established that Ip stimulated erythropoiesis pr i ­mari ly by its direct influence on the bone marrow (6). I t is a noteworthy fact that along wi th E p reduction there is also I E which probably contributes to the totally lower plasma E p ac t iv i ty . I E appearance can be explained wi th the higher levels of erythrocytes and haemoglobin estab­lished (6) which could as well inhibit E p production, as stimulate an inhibitor appearance by a feedback mechanism (24). The comparison of E p act iv i ty in animals treated wi th Pr and of that in control shows a tendency to levels lower by 17,04 % . Th i s is considered to be due to the presence of I E (fig. 3b) which takes part in determination of total plas­ma ac t iv i ty . According to our opinion, one of the factors which could stimulate I E production by a feed-back mechanism is the increased reticulocyte count. I t is possibly that the lower plasma E p acti­v i t y as compared wi th the control one is due also to the inhibited E p production, as far as it is known that Pr inhibits a number of metabolic processes (8,20). T h i s P r effect is probably mediated by cAMP which is considered to be playing i 15,86 Ep Standard „C 5 1 10 ^ " / 5 | Fig . За, Plasma inhibitory properties of Isoprenaline-treated rats. B y the ordinate to the left — % of the incorporated b 9 F e in polycytemic rats under the influence of 0,5E Ep standard «C» to the right — % of inhi­bition compared to the Ep standard «C» un­der the influence of the investigated plasma. F ig . 3b. Plasma inhibitory properties of Propranolol-treated rats. The same indica­tions. an important role in E p biogenesis (18,26). The data concerning plasma E p ac­t iv i ty in rats treated wi th Pr and Ip both represent a certain interest. The jux ta ­position of this ac t iv i ty wi th that of con­trol plasma shows a diminution of 15,23 % while in Ip treated animals this reduction is 32,97 % (fig. 2) . According to us this considerable inhibition of Ip effect after a preliminary beta-adrenoblockade also points to the fact that the beta-adrenoreceptors participate in E p biogenesis in these conditions. A t present, the precise mechanism of this action couldn't be easily explained. cAMP may also take part here. However, according to us it is more l ikely that P r could reduce the renal blood flow (7, 9, 27) and it can increase renal E p production by the way of relative renal hypoxia (17). The tendency to increased E p ac t iv i ty in rats treated wi th R (fig. 1 ,2 ) is due, according to us, to its increased production on the one hand, and to its in­hibited ut i l izat ion, on the other one. Catecholamines depletion (17) which oc-Plasma erythropoietin activity and. curs in the in i t ia l phase of adrenergic post-reserpine blockade could reduce re­nal blood flow (22) and hence increase E p production. The markedly low 5 9 F e incorporation into erythrocytes, the reduction of both reticulocytes and myelocaryocytes (6) speaks for a low functional ac t iv i ty of bone marrow erythroblasts, respectively, for inhibited E p realization. According to opinion a l l this can cause the higher E p ac t iv i ty in R treated rats. Our data are in concordance wi th the results of Gubina et a l . (1974) who have found an E p increase after renal denervation. Our results confirm the important role of the adrenergic system in E p acti­v i ty and I E regulation, i . e. in the maintenance of erythrocyte homeostasis. Of course, this regulation is complex and is closely related to total metabolism (6). The feed-back mechanism may play an important role in this regulation. I t is bound up not only wi th stimulation or suppression of E p production but also wi th the presence of I E . R E F E R E N C E S 1. Б а р к о в а , H . В: Физиология эритропоэза. Л . , Наука , 1979, 97—117. — Г у д и м , В . И., Г. П. М о с к а л е в а , Т. И. К о р е ц к а я и д р . Пробл. ге-атол. и перелив, крови, 1971, 10, 48—49. — З . Г у д и м , В . И. , Г. П. М о с к а л е ­в а , В. С. И в а н о в а . Бюлл. эксперим. биол. и мед., 1974, 7, 28—30. — 4. 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Eriedberg/Hessen, 1978, 113 — 116. — 26. R o d g e r s -G . M. , J . W. F i s h e r , W. J . G e o r g e . Amer. J . Med., 58, 1975, 31—38. — 27. S o l , t i , F . , J . K a s z o n a i , J . R е i , J . N a g i . Acta Physiol. Acad. Sci. Hung., 38, 1970 85—92. 44 1 Т. Ganchev, М. Georgieva ЭРИТРОПОЭТИНОВАЯ АКТИВНОСТЬ И ИНГИБИТОРНЫЕ СВОЙСТВА ПЛАЗМЫ КРЫС ПОСЛЕ РАЗЛИЧНЫХ АДРЕНЕРГИЧЕСКИХ ВОЗДЕЙСТВИЙ Т. Ганчев, М . Георгиева Р Е З Ю М Е Изучается эритропоэтиновая активность и ингибиторные свойства плазмы после раз­личных своим механизмом водействий на адренергическую систему крыс. Бета-адреностимуляция изопреналином понижает эритропоэтиновую активность по отношению к контролю на 32,97 % и показывает ингибицию на 7,07 %. Частичное снятие изопреналинового эффекта после предварительной бета-адреноблокады пропранололом (от 32,97 % до 15,32 % ) свидетельствует об участии бета-адренорецепторов в биогенезе эритро-поэтина. Бета-адреноблокада пропранололом понижает активность эритропоэтина на 17,04 % и выявляет ингибирующие свойства плазмы — 15,86 %. Подавление невронального звена адренергической медиаторной единицы резерпином вызывает увеличение плазменного эритро­поэтина на 24,92 %. Подчеркивается важная роль адренергической системы в регуляции плазменного эритропоэтина и ингибитора эритропоэза. 

PLASMA ERYTHROPOIETIN ACTIVITY AND INHIBITORY PROPERTIES AFTER VARIOUS ADRENERGIC INFLUENCES IN RATS

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PLASMA ERYTHROPOIETIN ACTIVITY AND INHIBITORY PROPERTIES AFTER VARIOUS ADRENERGIC INFLUENCES IN RATS

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