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Biomedical subjects

T Godfraind

Publications and source records attributed to T Godfraind.

At least 127 records · Page 7Linked to original sources
PubMed1984

Sodium/calcium exchange in smooth-muscle microsomal fractions.

The existence of Na+ -dependent Ca2+ transport was investigated in microsomal fractions from the longitudinal smooth muscle of the guinea-pig ileum and from the rat aorta, and its activity was compared with that of the plasmalemmal ATP-dependent Ca2+ pump previously identified in these preparations. The rate of Ca2+ release from plasmalemmal vesicles previously loaded with Ca2+ through the ATP-dependent Ca2+ pump was transiently faster in the presence of 150 mM-NaCl in the medium than in the presence of 150 mM-KCl or -LiCl or 300 mM-sucrose. Na+-loaded vesicles took up Ca2+ when an outwardly directed Na+ gradient was formed across the membrane. The Ca ionophore A23187 induced a rapid release of 85% of the sequestered Ca2+, whereas only 15% was displaced by La3+. Ca2+ accumulated by the Na+-induced Ca2+ transport was released by the addition of NaCl, but not KCl, to the medium. Ca2+ uptake in Na+-loaded vesicles was inhibited in the presence of increasing NaCl concentration in the medium. Half-maximum inhibition was observed with 28 mM-NaCl. Data fitted the Hill equation, with a Hill coefficient (h) of 1.9. Na+-induced Ca2+ uptake was a saturable function of Ca2+ concentration in the medium. Half-maximum activity was obtained with 18 microM-Ca2+ in intestinal-smooth-muscle microsomal fraction and with 50 microM-Ca2+ in aortic microsomal fraction. The results suggest that in these membrane preparations a transmembrane movement of Ca2+ can be driven by a Na+ gradient. However, the Na+-induced Ca2+ transport had a lower capacity, a lower affinity and a slower rate than the ATP-dependent Ca2+ pump.

Adenosine Triphosphate↗
PubMed1984

Heterogeneity of ouabain specific binding sites and (Na+ + K+)-ATPase inhibition in microsomes from rat heart.

Cardiac glycoside binding to microsomes prepared from rat heart ventricles and enriched in (Na+ + K+)-ATPase was measured by a rapid filtration technique. The relation between ouabain binding to microsomes and (Na+ + K+)-ATPase activity has also been examined. Data were statistically analysed by means of two different non linear regression methods. The experimental results were fitted the most closely by a model describing that ouabain specific binding occurred at two classes of independent sites. High affinity sites were characterized by a dissociation constant of 0.21 +/- 0.01 microM and a low capacity (9.4 +/- 1.4 pmoles/enzymatic unit). Low affinity sites were characterized by a dissociation constant equal to 13 +/- 3 microM and a capacity equal to 87 +/- 15 pmoles/enzymatic unit. Similar results were obtained with the more lipophilic glycoside digoxin. It was also observed that dihydroouabain, a ouabain derivative with a saturated lactone ring, competes with 3H-ouabain for the binding to the two classes of sites. Binding to these two classes of sites appeared to be associated with a corresponding inhibition of (Na+ + K+)-ATPase activity.

Animals↗
PubMed1984

Enhanced responsiveness of rat isolated aorta to clonidine after removal of the endothelial cells.

With the endothelium present, the maximum response of rat isolated aorta to clonidine was much lower than that to noradrenaline. Removal of endothelium enhanced the response to both adrenoceptor agonists and the clonidine-induced maximum contraction became almost equal to that produced by noradrenaline, although it was much more sensitive to inhibition by flunarizine and nifedipine. These results indicate that clonidine and noradrenaline activate receptors present in the endothelial cells and that these receptors are highly sensitive to clonidine.

Animals↗
PubMed1984

[Severe hypertrophic myocardiopathy in newborn infants. Intra-erythrocyte calcium and the effect of lidoflazine, a calcium-channel inhibitor. Apropos of 2 cases].

Two cases of severe hypertrophic obstructive cardiomyopathy in the neonate are reported. The first case was poorly tolerated because of predominant stenosis of the right ventricular outflow tract causing right to left shunting through a patent foramen ovale. The second case presented with severe syncope at 6 weeks of age. The first patient was treated with propranolol without any success. Regression of the clinical and electrocardiographic signs was obtained in both cases with lidoflazine, within a few weeks. Red blood cell calcium concentrations were abnormally high in both patients before treatment and returned to normal levels with clinical and echocardiographic improvement. Abnormal accumulation of intracellular calcium in the myocardium is a possible mechanism of this cardiomyopathy. The relation between this type of accumulation and the effects of catecholamine discharge are recalled. The possible initiating role of an enzymatic abnormality of calcium entry is discussed: the chaotic geometric alignment of the myocardial fibres, characteristic of this type of hypertrophy, would therefore be a secondary phenomenon. Once constituted, the hypertrophy would then become irreversible. However, it may be possible to reverse it in the neonate by calcium antagonists as suggested by these two cases.

Calcium↗
PubMed1984

Action of creatinol-O-phosphate on the contractility changes evoked by hypoxia and ischemia in rat isolated heart.

The effect of creatinol-O-phosphate (N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate, creatinolfosfate, Aplodan) pretreatment has been studied on the recovery of contractility of rat isolated heart after hypoxia or ischemia. In normoxia creatinol-O-phosphate (100 mumol/l) evoked a positive inotropic effect only when glucose was present in the physiological solution, it also evoked a slight negative chronotropic effect that was independent of glucose. When creatinol-O-phosphate was present during hypoxia, in the physiological solution, the recovery of the contraction after reoxygenation (in the absence of the drug) was improved in a dose-dependent manner. When creatinol-O-phosphate was present in the physiological solution before ischemia, the recovery of the contractility after reperfusion was higher than in controls; the presence of creatinol-O-phosphate during reperfusion after ischemia accelerated the recovery of contractility. The action of creatinol-O-phosphate on the recovery of cardiac contractility after ischemia was also observed in hearts partially protected with a cardioplegic solution. It is suggested that creatinol-O-phosphate could exert its cardioprotective effect by an action on anaerobic glycolysis.

Animals↗
PubMed1984

Contractile activity of human coronary arteries and human myocardium in vitro and their sensitivity to calcium entry blockade by nifedipine.

Depolarization (100 mM K+) of acetylcholine, serotonin and prostaglandin (PG) F2 alpha contracted human isolated coronary artery segments. Serotonin was about 10-fold more potent than either acetylcholine or PGF2 alpha, but PGF2 alpha elicited contractions of the greatest magnitude. Serotonin (10 microM) and PGF2 alpha (3 microM) induced rhythmic contractions in the arterial segments. Depolarization-, PGF2 alpha- and serotonin-induced increase in tone was depressed by nifedipine, as was the serotonin- and PGF2 alpha -induced rhythmic activity. The induced rhythmic activity was about 100-fold more sensitive to inhibition by nifedipine than was the induced tonic contraction of the arteries. Depolarization-induced contractions and serotonin-induced rhythmic contractions displayed about equal sensitivity to inhibition by nifedipine. Nifedipine was more potent as an inhibitor of depolarization-induced contractions of arteries than it was as an inhibitor of electrically stimulated trabecular strips of ventricle from the same hearts. The inhibition of isolated coronary artery contraction was obtained within the range of nifedipine concentrations observed in the blood of treated patients.

Acetylcholine↗
PubMed1984

Drug-induced cardionecrosis.

Cardiotoxicity may be defined as a drug action producing abnormalities in cardiac function, such as transitory disturbances or rhythm, conduction or contractility. Clearance of the drug is followed by recovery of the initial function. Cardionecrosis is the irreversible consequence of cardiotoxicity. Its appearance depends not only upon the toxicological potency of a given compound but may also depend upon the pathophysiological state of the heart. Therefore, two main categories may be recognized considering the influence of this state. Drugs may act on the processes controlling cellular structure such as protein biosynthesis in the case of antibiotics of the anthracycline group. Drugs may act at the level of metabolic regulation through a membranal or an intracellular action; in this case, the functional state of the heart plays a major role. This is mainly observed with sympathomimetics and with drugs interacting with the function of catecholamines. The cardiotoxicity observed in such conditions mimics the action of anoxia or of ischemia. The main determinant of the cardiac lesion is probably the disturbance of cellular calcium metabolism. This situation may be prevented (or treated) by the use of calcium entry blockers (calcium antagonists). A great part of this report will deal with the second group of drugs, because of their potential importance as a chemical hazard for the population and because of a possible preventive protection by calcium entry blockers (calcium antagonists).

Anesthetics↗
PubMed1983

The action of tabernanthine on noradrenaline-stimulated contractions and 45Ca movements in rat isolated vascular smooth muscle.

The iboga alkaloid tabernanthine inhibited depolarization (100 mM K+)-induced contractions in aorta and mesenteric arteries in an concentration-dependent manner with the respective IC50 values being about 21 and 7 microM. Contractions elicited by noradrenaline in the mesenteric artery were potentiated by lower concentrations (0.1 and 1.0 microM) of tabernanthine while they were inhibited by higher concentrations (10-100 microM). Tabernanthine produced only inhibition of noradrenaline-elicited responses in aorta and portal vein, the vein being the most sensitive of the vessels to the inhibitory effects of the compound. The magnitude of the spontaneous contractions of the portal vein, the aortic intracellular calcium fraction releasable by noradrenaline and the turnover of calcium in unstimulated aorta were enhanced by tabernanthine. Depolarization-stimulated 45Ca influx and contractions in the aorta were inhibited to a similar extent by tabernanthine and 100 microM virtually abolished the 45Ca influx stimulated by noradrenaline and depolarization. It is concluded that tabernanthine has a calcium entry blocking action but also has other actions related to the turnover of intracellular calcium releasable by noradrenaline.

Alkaloids↗
PubMed1983

The inotropic effect of ouabain and its antagonism by dihydroouabain in rat isolated atria and ventricles in relation to specific binding sites.

The inotropic effect of ouabain has been studied in rat ventricles and atria. The concentration-effect curve of ouabain may be fitted by a model assuming the existence of two saturable components. The component with the higher sensitivity to ouabain accounted for 30% of the maximal increase in systolic tension in ventricles and for only 5% in atria. Increase in diastolic tension was only apparent at ouabain concentrations required to observe the low sensitivity component. [3H]-ouabain binding has been examined in microsomes prepared from atria and ventricles. High and low affinity binding sites have been observed. The ratio of high and low affinity ouabain binding sites was 4 fold lower in microsomes from rat atria than from rat ventricles. This could account for the difference in the response of these two tissues to the inotropic action of ouabain. In ventricular strips the high sensitivity component was much less apparent in the presence of dihydroouabain than with ouabain. When ventricular strips were preincubated in the presence of dihydroouabain 3 microM, the increase in systolic tension evoked by ouabain 1 microM was significantly reduced. Cumulative concentration-effect curve studies showed dihydroouabain antagonism to the high sensitivity component.

Animals↗
PubMed1983

Effects of histamine and the histamine antagonists mepyramine and cimetidine on human coronary arteries in vitro.

The effects of histamine have been studied on human isolated coronary artery preparations taken from hearts ranging in age from 9 to 73 years. Histamine in large concentrations (100 microM) contracted arteries which were without tone or spontaneous activity and sometimes induced rhythmic contractile activity. If spontaneous rhythmic activity was present it was enhanced by histamine. The contractile effects of histamine were inhibited by mepyramine but not by cimetidine. Arteries which were contracted by depolarization responded with relaxation to histamine concentrations lower than those required to evoke a contraction; arteries from younger hearts were more sensitive than those from older hearts. Mepyramine potentiated the maximal relaxant effect of histamine in arteries from hearts of all ages but cimetidine had very little effect. In the presence of mepyramine, cimetidine antagonized the relaxant effect of histamine, shifting the concentration-effect curve to the right. It is concluded that human coronary arteries contain both H1- and H2-type receptors, the H1-receptors mediating contraction. The relaxant effects of histamine can only be inhibited by a combination of both H1- and H2-receptor antagonists.

Adolescent↗
PubMed1983

Effects of yohimbine, rauwolscine and corynanthine on contractions and calcium fluxes induced by depolarization and prostaglandin F2 alpha in rat aorta.

The effects of the selective alpha 2-adrenoceptor antagonists yohimbine and its stereo-isomer rauwolscine and the selective alpha 1-adrenoceptor antagonist corynanthine (a third yohimbine stereoisomer) on contractions induced in rat aorta by depolarization and prostaglandin F2 alpha (PGF2 alpha) have been compared. In calcium-free solution, depolarization with 100 mM K+ failed to produce a contraction of rat aorta but PGF2 alpha (3 microM) stimulated a contraction equal to about 23% of maximal elicited in normal physiological solution. Yohimbine had no significant effect on depolarization-induced contractions except at concentrations greater than 30 microM. Rauwolscine and corynanthine (1 to 100 microM) depressed depolarization-induced contractions in a concentration-dependent manner, but the characteristics of inhibition were not identical. Contractions induced by PGF2 alpha (3 microM) were depressed in a concentration-dependent manner by rauwolscine (3 to 100 microM) but were unaffected by yohimbine or corynanthine. Depolarization-stimulated 45Ca influx was depressed by rauwolscine and corynanthine to about the same extent as were the contractions; while rauwolscine (100 microM) completely inhibited PGF2 alpha-stimulated 45Ca influx, it also depressed part of the PGF2 alpha-stimulated contraction dependent on intracellular calcium. Rauwolscine (100 microM) partly inhibited PGF2 alpha-stimulated release of 45Ca from aortic smooth muscle in calcium-free solution. It is concluded that the yohimbine structure possesses a calcium entry blocking action as well as a depressant action on contractions not dependent on calcium entry. The predominant effect depends on the structural configuration and the nature of the stimulating agent.

Animals↗