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Increased sensitivity to nifedipine of smooth muscle from hypertensive rats cannot beexplained by calcium influx blockage
j Mol Cell Cardiol 18 (Supplement 3) (1986) INCREASED SENSITIVITY TO NIFEDIPINE OF SMOOTHMUSCLE FROMHYPERTENSIVE RATS CANNOTBE EXPLAINED BY CALCIUM INFLUX BLOCKAGE. H.E. Cingolani, G.J. Rinaldi, E. Amado Cattaneo and A. M a t t i a z z i . Centro de Investigaciones Cardiovasculares, Facultad de Ciencias M~dicas, Universidad Naciona] de La P l a t a , 60 y 120,(1900) La P l a t a , A r g e n t i n a . A o r t i c smooth muscle i s o l a t e d from spontaneously h y p e r t e n s i v e rats (SHR) and Wistar Kyoto rats (WKY), was precontracted by KCI. The r e l a x a n t e f f e c t of n i f e d i p i n e (N) was more pronounced in SHR than in WKY, w h i l e the r e l a x a t i o n produced by n i t r o g l y c e r i n
(NTG) was similar in both tissues. EC50s were (in -log IMI): N: SHR 13.1 • 0.4, WKY 9.4• (P
DIRECT ANABOLIC EFFECT OF GLUCOCORTICOIDS ON CARDIAC PROTEIN SYNTHESIS: SELECTIVE ACTION ON CONTRACTILE PROTEINS. Abbot F. Clark, Kern Wildenthal. Dept. Physiology, University of Texas Health Science Center at Dallas, Texas 75235 In contrast to t h e i r well-known catabolic effect in skeletal muscle, glucocorticoids are anabolic for the heart in vivo. We have sought to determine i f this is a direct or indirect effect and i f certain proteins are affected p r e f e r e n t i a l l y . Rats received daily injections of dexamethasone (DEX) for two days and cardiac protein synthesis was measured in a t r i a l explants and in Langendorff perfused hearts. The hearts of DEX-treated animals were s i g n i f i c a n t l y larger than controls (+6%) presumably due to the observed increase in the rate of t o t a l cardiac protein synthesis (+14 + 4.5%). Not a l l cardiac proteins were s i m i l a r l y affected: the synthesis of Cardiac myosin and actin was disproportionately increased by 24 + 7.0% and 55 + 12.9%, respectively. In separate experiments, we tested the direct ~ffect of hydr~cortisone in isolated mouse hearts in organ culture. Incubation with hydrocortisone for 24 hours resulted in a significant increase in myosin and actin synthesis (+28 + 5.8% and +22 + 8.5%, respectively) while t o t a l protein synthesis remained unaltered (+5 + 3.0%)~ This selective effect was expressed in the presence or absence of insulin. Thus, glucocorticoids act rapidly (24-48 hrs) and d i r e c t l y on the heart, by selectively increasing the rates of myosin and actin synthesis.
MULTIPLE SITES OF MODULATION OF CALCIUM ION MOVEMENTS IN CARDIAC TISSUE: IMPLICATIONS FOR CARDIAC ARRHYTHMIAS. WA Coetzee, LH Opie, FT Thandroyen, University of Cape Town, South Africa. Abnormal control of calcium ion movements may contribute to the genesis of ventricular arrhythmias by the following mechanisms: (i) calcium-induced uncoupling between c e l l s , ( i i ) sustained calcium overload with enhanced ischemic depolarization and ( i i i ) o s c i l l a t o r y calcium ion movements predisposing to delayed afterdepolarizations. The most common therapeutic site of calcium ion modulation is by slow channel i n n i b i t i o n which can only improve calcium overload should the source of the calcium be external. Diltiazem 1 uM can modulate ischemic ventricular f i b r i l l a t i o n in the absence of changes in coronary flow or tissue metabolism (fixed low-flow guinea-pig ischemia), probably by decreasing ischemic conduction delay. Sarcoplasmic calcium ion o s c i l l a t i o n s appear to underlie the development of delayed afterdepolarizations (DADs) w h i c h can be evoked by dibutyryl cyclic AMP and inhibited by metabolic inhibitors. Energy is required and DADs are most l i k e l y to underlie reperfusion arrhythmias and not those of severe ischemia, l{yanodine and caffeine i n n i b i t ischemic arrhythmias showing that calcium ion movements in and out of the sarcoplasmic reticulum must be involved, and that requires energy. Presumably such ventricular arrhythmias are generated in those ischemic cells s t i l l capable of ATP synthesis. 1332A
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(NTG) was similar in both tissues. EC50s were (in -log IMI): N: SHR 13.1 • 0.4, WKY 9.4• (P
DIRECT ANABOLIC EFFECT OF GLUCOCORTICOIDS ON CARDIAC PROTEIN SYNTHESIS: SELECTIVE ACTION ON CONTRACTILE PROTEINS. Abbot F. Clark, Kern Wildenthal. Dept. Physiology, University of Texas Health Science Center at Dallas, Texas 75235 In contrast to t h e i r well-known catabolic effect in skeletal muscle, glucocorticoids are anabolic for the heart in vivo. We have sought to determine i f this is a direct or indirect effect and i f certain proteins are affected p r e f e r e n t i a l l y . Rats received daily injections of dexamethasone (DEX) for two days and cardiac protein synthesis was measured in a t r i a l explants and in Langendorff perfused hearts. The hearts of DEX-treated animals were s i g n i f i c a n t l y larger than controls (+6%) presumably due to the observed increase in the rate of t o t a l cardiac protein synthesis (+14 + 4.5%). Not a l l cardiac proteins were s i m i l a r l y affected: the synthesis of Cardiac myosin and actin was disproportionately increased by 24 + 7.0% and 55 + 12.9%, respectively. In separate experiments, we tested the direct ~ffect of hydr~cortisone in isolated mouse hearts in organ culture. Incubation with hydrocortisone for 24 hours resulted in a significant increase in myosin and actin synthesis (+28 + 5.8% and +22 + 8.5%, respectively) while t o t a l protein synthesis remained unaltered (+5 + 3.0%)~ This selective effect was expressed in the presence or absence of insulin. Thus, glucocorticoids act rapidly (24-48 hrs) and d i r e c t l y on the heart, by selectively increasing the rates of myosin and actin synthesis.
MULTIPLE SITES OF MODULATION OF CALCIUM ION MOVEMENTS IN CARDIAC TISSUE: IMPLICATIONS FOR CARDIAC ARRHYTHMIAS. WA Coetzee, LH Opie, FT Thandroyen, University of Cape Town, South Africa. Abnormal control of calcium ion movements may contribute to the genesis of ventricular arrhythmias by the following mechanisms: (i) calcium-induced uncoupling between c e l l s , ( i i ) sustained calcium overload with enhanced ischemic depolarization and ( i i i ) o s c i l l a t o r y calcium ion movements predisposing to delayed afterdepolarizations. The most common therapeutic site of calcium ion modulation is by slow channel i n n i b i t i o n which can only improve calcium overload should the source of the calcium be external. Diltiazem 1 uM can modulate ischemic ventricular f i b r i l l a t i o n in the absence of changes in coronary flow or tissue metabolism (fixed low-flow guinea-pig ischemia), probably by decreasing ischemic conduction delay. Sarcoplasmic calcium ion o s c i l l a t i o n s appear to underlie the development of delayed afterdepolarizations (DADs) w h i c h can be evoked by dibutyryl cyclic AMP and inhibited by metabolic inhibitors. Energy is required and DADs are most l i k e l y to underlie reperfusion arrhythmias and not those of severe ischemia, l{yanodine and caffeine i n n i b i t ischemic arrhythmias showing that calcium ion movements in and out of the sarcoplasmic reticulum must be involved, and that requires energy. Presumably such ventricular arrhythmias are generated in those ischemic cells s t i l l capable of ATP synthesis. 1332A
19