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Comparison of cardiac and vascular properties of ouabain and the aminosteroid LND 796 in guinea pigs
J Mol
Cell
Cardiol
23 (Supplement
IV)
(1991)
154 COMPARISON OF THE RATIO BETWEEN RYANODINE- AND DHP-RECEPTORS IN GUINEA
PIG AND RAT HEARTS. F. Rannou, C. Sainte-Beuve, I. Primot, P. Oliviero, D. Charlemagne. INSERM U 127, Hopital Lariboisike, 75010 Paris, France. To determine whether the relative contribution of calcium inflw from the sarcolemma (SL) and calcium release from the sarcoplasmic reticulum (SR) to the increase in [Cali was related to the number or ratio of DHP- and Ryanodine receptors in the heart from different species, we have compared the density and affinity of these receptors in cardiac membranes from guinea pig and rat because it is well known that the guinea pig heart exhibited a higher contribution of the SL and a lower of the SR than the rat heart. Binding assays were performed with [3H]PN 200-110 and [3H]Ryanodine on crude membrane preparations which contain 100 I of the receptors and analysed by Scatchard plots. Our results indicate that in guinea pig and rat left ventricle (LV) the number of DHP receptors per g of LV (13906f846 and 13724zt2430 fmol, respectively) and the number of Ryanodine receptors (3 135Oi7750 and 28605f6590 fmol, respectively) were similar. Thus the density and the ratio of these receptors were unchanged in guinea pig and rat LV and cannot account for the differences observed in their participation in the [Cali incrcase. These results do not preclude the possibility that their activity or regulation are different. It will be interesting to determine if the ratio between Ryanodine- and DHP receptors is modified in guinea pig and rat heart during adaptation to pressure overload.
155
ANTIOXIDANT DEFICIENCY AFTER HEART TRANSPLANTATION. A. Favier and S. Renaud. Laboratory of Biochemistry, Cardiovascular Hospital, Lyon - France.
CHU
M.J. Richard, Grenoble
M. de Lorgeril, and INSERM
J. Amaud, U.63 and
Accelerated coronary artery disease (CAD) has emerged as a major limitation to the long-term success of heart transplantation (HT). To test the hypothesis that antioxidant defenses are not adequate after HT, we have measured plasma concentrations of vitamin E (E), hydroperoxides (HPO), malondialdehyde (MDA), Selenium (Se), Zinc (Zn), Copper (Cu), glutathion peroxidase and superoxide dismutase in 15 consecutive, cyclosporine-treated HT recipients and 15 healthy comparable conlrols. The 2 groups were different with regards to Chol (5.1tO.2 mmol/L vs 6.7kO.4, p=O.O02), triglycerides (0.9~0.06mmol/L vs 2.6f0.7, p=O.O2), non HDL-Chol (3.6f0.2 mmol/L vs 5.4f0.4, p=O.OOl) and creatinine (99.8f4.5 mmol/L vs 127.1f4.9, p=O.OOl). When related lo non-HDL Chol, E was significantly lower in HT recipients (2.05iO.08 mg/l vs 1.75M.11, p=O.O4). In addition, HP0 were higher (122f8 pmoles/L vs 174fl1, p=O.O02) and Zn was lower (12.2f0.3 pmoles/L vs 9.3f0.5, p=O.OOOi) in HT patients whereas MDA, Se, Cu and other enzymes were similar. Finally, when the 2 groups were pooled, creatinine appeared to be correlated positively with HP0 (r=+0.46, p=O.Ol) and negatively with Zn (r=-0.51, p=O.O04) suggesting that Zn deficiency and increased hydroperoxides are linked to renal dysfunction. It is concluded that after HT, antioxidant defenses are deficient.
156
COMPARISON OF CARDIAC AND VASCULAR PROPERTIES OF OUABAIN AND THE AMINOSTEROID 796 IN GUINEA PIGS. D. Roeher, Ph. Lechat, DBpartement de Pharmacologic. CHU Pitie SalpBtriBre, Paris, France.
LND
Digitalis clinical use is limited by a narrow therapeutic index. Aminosteroid drugs represent a new class of compounds which inhibit (Na-K) ATPase with a larger range of doses between those inducing purely positive cardiac inotropic effects and those inducing toxicity. We compared oubaln (0) properties to those of the aminosteroid LND 796 (LN) in vitro on the isolated isovdumetrkzally working heart and aortic rings from guinea pigs. 0 and LN induced a maximum positive inotropic effect to a similar extend + 172% f 27 (0) versus +209%&j (LN) for increase of left ventricular pressure (LVP) dp/dt max, but with higher doses for LN (4.5x10-6M f. 0.4) versus 0 (7.2x10-7M f 0.4), p
Cell
Cardiol
23 (Supplement
IV)
(1991)
154 COMPARISON OF THE RATIO BETWEEN RYANODINE- AND DHP-RECEPTORS IN GUINEA
PIG AND RAT HEARTS. F. Rannou, C. Sainte-Beuve, I. Primot, P. Oliviero, D. Charlemagne. INSERM U 127, Hopital Lariboisike, 75010 Paris, France. To determine whether the relative contribution of calcium inflw from the sarcolemma (SL) and calcium release from the sarcoplasmic reticulum (SR) to the increase in [Cali was related to the number or ratio of DHP- and Ryanodine receptors in the heart from different species, we have compared the density and affinity of these receptors in cardiac membranes from guinea pig and rat because it is well known that the guinea pig heart exhibited a higher contribution of the SL and a lower of the SR than the rat heart. Binding assays were performed with [3H]PN 200-110 and [3H]Ryanodine on crude membrane preparations which contain 100 I of the receptors and analysed by Scatchard plots. Our results indicate that in guinea pig and rat left ventricle (LV) the number of DHP receptors per g of LV (13906f846 and 13724zt2430 fmol, respectively) and the number of Ryanodine receptors (3 135Oi7750 and 28605f6590 fmol, respectively) were similar. Thus the density and the ratio of these receptors were unchanged in guinea pig and rat LV and cannot account for the differences observed in their participation in the [Cali incrcase. These results do not preclude the possibility that their activity or regulation are different. It will be interesting to determine if the ratio between Ryanodine- and DHP receptors is modified in guinea pig and rat heart during adaptation to pressure overload.
155
ANTIOXIDANT DEFICIENCY AFTER HEART TRANSPLANTATION. A. Favier and S. Renaud. Laboratory of Biochemistry, Cardiovascular Hospital, Lyon - France.
CHU
M.J. Richard, Grenoble
M. de Lorgeril, and INSERM
J. Amaud, U.63 and
Accelerated coronary artery disease (CAD) has emerged as a major limitation to the long-term success of heart transplantation (HT). To test the hypothesis that antioxidant defenses are not adequate after HT, we have measured plasma concentrations of vitamin E (E), hydroperoxides (HPO), malondialdehyde (MDA), Selenium (Se), Zinc (Zn), Copper (Cu), glutathion peroxidase and superoxide dismutase in 15 consecutive, cyclosporine-treated HT recipients and 15 healthy comparable conlrols. The 2 groups were different with regards to Chol (5.1tO.2 mmol/L vs 6.7kO.4, p=O.O02), triglycerides (0.9~0.06mmol/L vs 2.6f0.7, p=O.O2), non HDL-Chol (3.6f0.2 mmol/L vs 5.4f0.4, p=O.OOl) and creatinine (99.8f4.5 mmol/L vs 127.1f4.9, p=O.OOl). When related lo non-HDL Chol, E was significantly lower in HT recipients (2.05iO.08 mg/l vs 1.75M.11, p=O.O4). In addition, HP0 were higher (122f8 pmoles/L vs 174fl1, p=O.O02) and Zn was lower (12.2f0.3 pmoles/L vs 9.3f0.5, p=O.OOOi) in HT patients whereas MDA, Se, Cu and other enzymes were similar. Finally, when the 2 groups were pooled, creatinine appeared to be correlated positively with HP0 (r=+0.46, p=O.Ol) and negatively with Zn (r=-0.51, p=O.O04) suggesting that Zn deficiency and increased hydroperoxides are linked to renal dysfunction. It is concluded that after HT, antioxidant defenses are deficient.
156
COMPARISON OF CARDIAC AND VASCULAR PROPERTIES OF OUABAIN AND THE AMINOSTEROID 796 IN GUINEA PIGS. D. Roeher, Ph. Lechat, DBpartement de Pharmacologic. CHU Pitie SalpBtriBre, Paris, France.
LND
Digitalis clinical use is limited by a narrow therapeutic index. Aminosteroid drugs represent a new class of compounds which inhibit (Na-K) ATPase with a larger range of doses between those inducing purely positive cardiac inotropic effects and those inducing toxicity. We compared oubaln (0) properties to those of the aminosteroid LND 796 (LN) in vitro on the isolated isovdumetrkzally working heart and aortic rings from guinea pigs. 0 and LN induced a maximum positive inotropic effect to a similar extend + 172% f 27 (0) versus +209%&j (LN) for increase of left ventricular pressure (LVP) dp/dt max, but with higher doses for LN (4.5x10-6M f. 0.4) versus 0 (7.2x10-7M f 0.4), p