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Endothelial cell injuries of coronary arteries in rats following burn
j Mol Cell Cardiol 19 (Supplement III) (1987)
271 SENSITIVITY OF RAT MYOCARDIUMTO OUABAIN IN ISOPROTERENOL-INOUCs CARDIAC HYPERTROPHY. J. SzabS, K. Nosztray, J. M@sz~ros, J. Szegi. Department of Pharmacology, University of Debrecen~ Oebrecen, Hungary
Medical
The myocardium of rats treated repeatedly with isoproterenol (IPR) has been shown to have reduced responsiveness to adrenergio stimulation. On the basis of a functional interrelationship between beta receptor-adenylate cyclase and dlgl alis receptor-Na , K§ the sensitivity of rat myocardium to ouabain in IPR-induced cardiac hypertrophy was studied. Left ventricular trabeeulae originating from IPR-treated rats were significantly less sensitive than controls to ouabain-induced positive inotropy. In crude homogenate and sarcolemmal fractions the ATP-hydrolysing activities both in the presence of Mg++("basic '') and Mg++,Na+,K+ ("total") were significantly reduced in the heart of IPR-~reated rats. However, the differencE between the total ATPase and Mg++ATPase (Na ,K -ATPase) and the sensitivity of Na ,K -ATPase to ouabain remained unchanged. The results indicate that the well-known relation of sodium pump inhibition to positive inotvopy ( J. Physiol. 360, 149-160, 1985 ) in the heart of IPR-treated rats may not be valid.
!72 Endothelial cell injuries of coronary arteries in rats following burn. K.Szab6, M.Farag6,
I.Balogh
B u r n Center of Central Hospital, Semmelweis Medical University 2nd Dept. of Physiology, Dept. of Forensic Medicine, Budapest, Mungary. Ultrastructural changes were found in myocardium of rats following burn. In the present work the authors studied morphological changes of the endothelial cells of the coronary arteries on isolated perfused rat hearts. 20-55% burned body surface scalding was induced in rats anesthetized with sodium pentobarbital. The animals were decapitated 2 hours, 2 and 7 days following scalding. The hearts were p e r f u s e d - f l x a t e d w i t h 3% glutaraldehlde and fixated with 1 % Os04. Myocardial samples were studied with JEM looB electronmlcroscope. By the 2nd p o s t b u r n hour endothelium swelling and pinocytosis were observed. By the 2nd day endothelial edema was of circular character obliterating the lumen; pinocytosls activity increased. By the 7th day obliteration became more pronounced, however, plnocytosls decreased. We suggest that n y p e r c a t e c h o l a m l n e m l a and release of other mediators following burn modify the regulation of coronary circulation.
73 ACTION DF PURINES ON THE ANAERDB FUNCTIONAL ACTIVITY OF GUINEA PIG HEART AND SKELETAL MUSCLE. J. Szegi, Agnes CseppentS, A.J. Szentmikl6si. Department of Pharmacology, Medical University of Debrecen, Debrecen, Hungary. The actions of purina derivatives on the heart and circulation have been extensively studied, however there is limited information on the direct effect of these substances on skeletal muscle. In the present study the actions of two alkylxanthines - aminophylline (APH), pentoxyphylline (PXPH) - and two nucleosides - adenosine (AR), inosine (INO) - were investigated in equimolar concentrations (lO0 umol/1) on the hypoxia-induced changes in contractility of myocardium (left atrium) and skeletal muscle (diaphragm). In a 8 min hypoxia period APH, pentoxyphylline and inesine inhibited the decrease of contractile force of atrial myocardium by 55.6, 27.6 and 10.7%, respectively. In the same conditions the % of inhibition of the hypoxia-induced impairment in skeletal muscle contractility were as follows: 27.8 (APH), 34.3 (PXPH), 32.3 (AR) and 14.3 (INO). None of these drugs per se did not influence the contractility of diaphragm. In myocardium aminophylline showed strong anti-AR action~ while PXPH (lO0 umol/l) did not affect the cardiodepressive effect of AR. It is concluded that the pronounced antihypoxic action of APH could be related to its ability in antagonizing the negative inotropic action of endoqenous AR, whereas in the other cases the mechanism underlying the muscle-protective acIion could be due to the metabolic activity of purine compounds.
S.91
271 SENSITIVITY OF RAT MYOCARDIUMTO OUABAIN IN ISOPROTERENOL-INOUCs CARDIAC HYPERTROPHY. J. SzabS, K. Nosztray, J. M@sz~ros, J. Szegi. Department of Pharmacology, University of Debrecen~ Oebrecen, Hungary
Medical
The myocardium of rats treated repeatedly with isoproterenol (IPR) has been shown to have reduced responsiveness to adrenergio stimulation. On the basis of a functional interrelationship between beta receptor-adenylate cyclase and dlgl alis receptor-Na , K§ the sensitivity of rat myocardium to ouabain in IPR-induced cardiac hypertrophy was studied. Left ventricular trabeeulae originating from IPR-treated rats were significantly less sensitive than controls to ouabain-induced positive inotropy. In crude homogenate and sarcolemmal fractions the ATP-hydrolysing activities both in the presence of Mg++("basic '') and Mg++,Na+,K+ ("total") were significantly reduced in the heart of IPR-~reated rats. However, the differencE between the total ATPase and Mg++ATPase (Na ,K -ATPase) and the sensitivity of Na ,K -ATPase to ouabain remained unchanged. The results indicate that the well-known relation of sodium pump inhibition to positive inotvopy ( J. Physiol. 360, 149-160, 1985 ) in the heart of IPR-treated rats may not be valid.
!72 Endothelial cell injuries of coronary arteries in rats following burn. K.Szab6, M.Farag6,
I.Balogh
B u r n Center of Central Hospital, Semmelweis Medical University 2nd Dept. of Physiology, Dept. of Forensic Medicine, Budapest, Mungary. Ultrastructural changes were found in myocardium of rats following burn. In the present work the authors studied morphological changes of the endothelial cells of the coronary arteries on isolated perfused rat hearts. 20-55% burned body surface scalding was induced in rats anesthetized with sodium pentobarbital. The animals were decapitated 2 hours, 2 and 7 days following scalding. The hearts were p e r f u s e d - f l x a t e d w i t h 3% glutaraldehlde and fixated with 1 % Os04. Myocardial samples were studied with JEM looB electronmlcroscope. By the 2nd p o s t b u r n hour endothelium swelling and pinocytosis were observed. By the 2nd day endothelial edema was of circular character obliterating the lumen; pinocytosls activity increased. By the 7th day obliteration became more pronounced, however, plnocytosls decreased. We suggest that n y p e r c a t e c h o l a m l n e m l a and release of other mediators following burn modify the regulation of coronary circulation.
73 ACTION DF PURINES ON THE ANAERDB FUNCTIONAL ACTIVITY OF GUINEA PIG HEART AND SKELETAL MUSCLE. J. Szegi, Agnes CseppentS, A.J. Szentmikl6si. Department of Pharmacology, Medical University of Debrecen, Debrecen, Hungary. The actions of purina derivatives on the heart and circulation have been extensively studied, however there is limited information on the direct effect of these substances on skeletal muscle. In the present study the actions of two alkylxanthines - aminophylline (APH), pentoxyphylline (PXPH) - and two nucleosides - adenosine (AR), inosine (INO) - were investigated in equimolar concentrations (lO0 umol/1) on the hypoxia-induced changes in contractility of myocardium (left atrium) and skeletal muscle (diaphragm). In a 8 min hypoxia period APH, pentoxyphylline and inesine inhibited the decrease of contractile force of atrial myocardium by 55.6, 27.6 and 10.7%, respectively. In the same conditions the % of inhibition of the hypoxia-induced impairment in skeletal muscle contractility were as follows: 27.8 (APH), 34.3 (PXPH), 32.3 (AR) and 14.3 (INO). None of these drugs per se did not influence the contractility of diaphragm. In myocardium aminophylline showed strong anti-AR action~ while PXPH (lO0 umol/l) did not affect the cardiodepressive effect of AR. It is concluded that the pronounced antihypoxic action of APH could be related to its ability in antagonizing the negative inotropic action of endoqenous AR, whereas in the other cases the mechanism underlying the muscle-protective acIion could be due to the metabolic activity of purine compounds.
S.91