Immunoelectron microscopic study on the atrial granules in canine atrial muscle cells

j Mol Cell Cardiol 19 (Supplement III) (1987)

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PATHOGENESIS OF ADRIAMYCIN CARDIOMYOPATHY I N NORMTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS (SHR) H.-a.Herrmann,S.Massow,V,Moritz,C.Norden,P.Mfihlig, Central Institute

for Heart and C i r c u l a t i o n R e s e a r c h B e r l i n and C e n t r a l I n s t i t u t e for M i c r o b i o l o g y and E x p e r i m e n t a l T h e r a p y Oena, A c a d e m y of S c i e n c e s , GDR The p a t h o m e c h a n i s m s u n d e r l y i n g the g e n e s i s of a d r i a m y c i n (ADR) c a 6 d i o m y o p a t h y end the role of h y p e r t e n s i o n as a risk factor of A D R - i n d u c e d heart i n s u f f i c i e n c y have not been e s t a b l i s h e d . T h e r e f o r e 21 172 1 - w e e k old SIIR and 18 n o r m o t e n s i v e W i s t a r rats (NWR) w e r e g i v e n 3 ore

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i n ~ e c t e d with s a l i n e . M y o c a r d i a l a l t e r a t i o n s were i n v e s t i g a t e d by m e a n s of e n z y m e h i s t o c h e m i c a l and h i s t o l o g i c a l s t a i n i n g m e t h o d s . Hietom o r p h o m e t r i c s t u d i e s in m l c r o v e s s e l s (my,) of the left v a n t r i c u l a r w a l l and the s k e l e t a l m u s c l e d e t e c t e d the e x i s t e n c e (NWR) end the inc r e a s e (SHR) of s t r u c t u r a l a d a p t a t i o n s t o c h r o n i c my. c o n t r a c t i o n s in the heart. In A D R - S H R b e s i d e s the w e l l - k n o w n single cell d e g e n e r a t i o n focal i s c h e m i c a l t e r a t i o n s c o u l d be i d e n t i f i e d t o p o l o g i c a l l y related t o t h e s e my. r e a c t i o n s and distinctly extended. These and further results document the p r e d o m i n a t i n g role of c h r o n i c c o r o n a r y my. con-

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CALCIUM ACTIVATION OF SKINNED FIBRES FROM CARDIOMYOPATHIC HAMSTER HEARTS ( BIO 14.6 ). J.W. Herzig, Dept. Research, Pharma D i v . , Ciba-Geigy L t d . , Basle, S w i t z e r l a n d . Skinned f i b r e s were prepared from normal ( RB ) and cardiomyopathic ( BlO 14.6 ) hamster v e n t r i c l e s using a d e t e r g e n t / g l y c e r o l e x t r a c t i o n technique. Calcium a c t i v a t i o n o f t e n s i o n was studied by v a r i a t i o n of pCa between 10 and 4.63, in presence o f 5 mM EGTA. The f o l l o w i n g f e a t u r e s were obtained: 1) The calcium s e n s i t i v i t y of t e n s i o n , measured as pCa f o r h a l f maximum calcium a c t i v a t i o n , was i n v a r i a b l y higher in l e f t than in r i g h t v e n t r i c u l a r skinned f i b r e s . 2) During progression of the cardiamyopothy w i t h age, t h e re was a r e d u c t i o n o f the maximum calcium a c t i v a t a b l e t e n s i o n , a phenomenon which appeared to be more pronounced in l e f t than in r i g h t v e n t r i c u l a r skinned f i b r e s . 3) The development of the cardiomyopathy hod no i n f l u e n c e on the calcium s e n s i t i v i t y of the skinned f i b r e s . 4) In skinned f i b r e s from l e f t and r i g h t v e n t r i c l e s , the development o f cardiomyopathy did not a f f e c t the calcium d e s e n s i t i z i n g e f f i c a c y o f cAMP. A l l these f i n d i n g s taken t o g e t h e r suggest t h a t t h e re i s no d i f f e r e n c e in the degree o f t r o p o n i o l p h o s p h o r y l a t i o n between skinned f i b r e s from h e a rt s of normal and cardiomyop a t h i c hamsters. The observed r e d u c t i o n in maximum calcium a c t i v a t a b l e tension may be a t t r i b u t e d to degenerative processes due to the i n c r e a s i n g c e l l u l a r calcium load during the development of h e r e d i t a r y cardiomyopathy.

I021NMUNOELECTRON MICROSCOPIC STUDY ON THE ATRIAL GRANULES IN CANINE ATRIAL MUSCLE CELLS. J. Hiroshige, Y. Takeyama, y. Suwa, S, Hasegawa, K. Umetsu, M. Mochizukf, K. Akiyama T. Katagiri, H. Niitani and Y. Nakai*. Third Department of Internal Medicine and Department of Anatomy*, Showa University School of Medicine, Tokyo, Japan. We investigated the distribution and the nature of atrial granules(AG) in canine atrial muscle cells by observation with an electron microscope. The changes in distribution of AG and in serum level of atrial natriuretie polypeptide(ANP) were also examined by atrial pacing. Dogs were divided into three groups, i.e., non-paced group (group A), paced for 20 m i n ~ r o u p B) and paced for 60 mine(group C). Hemodynamie parameters and serum ANPlevels were measured. Specimens' for immunocytoehemistry were obtained from tissues of atria and were prepared in a usual manneY except for immnocytochemieal reaction. AG, all of them specifically contained a number of gold particles of ANP, were obseryed scattered in the sarcoplasm of perinuclear, intermyofibrillar and suhsareolemmal area of atrial muse{e cells in group A. But in group B, AG were less numerous though we chanced to observe a 10t of immas AG budding from Golgi apparatus, suggesting the promotion of ANP secretion and production reflected by higher serum ANP level. On the contrary, AG were increased, especially in the Golgi's area and serum AMP level was lower in group C than in group B. From these results, it is confirmed that all the AG exclusively contained AMP and is suggested that the secretion of AMP from AG was accerelated by atrial pacing for 20 min, resulting from higher atrial pressures and that the produdtion of AG might be promoted for 60 mine

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