CARDIAC INTERACTION BETWEEN PARATHYROID HORMONE, β-ADRENOCEPTOR AGENTS, AND VERAPAMIL IN THE GUINEA-PIG IN VITRO

1. The present study examines the modulation, by parathyroid hormone, of the changes in myocardial contractile force induced by isoprenaline, propranolol isomers, verapamil, and nadolol. 2. Cardiac contractile force was estimated by the use of guinea-pig isolated auricles. Synthetic bovine 1-34 parathyroid hormone (sPTH) alone did not modify contractile force; conversely, sPTH significantly inhibited the cardiode-pressant effect of l-propranolol, d, l-propranolol, d-propranolol, and verapamil. These results suggested an action of sPTH independent of β-adrenoceptors. Against an hypothesis of a single, non-β-adrenoceptor mechanism of sPTH action on the heart are the following observations: (i) when β-adrenoceptors were blocked with nadolol, sPTH no longer inhibited the cardiodepressant effect of propranolol, (ii) sPTH reduced the inotropic effects of isoprenaline. Our conclusion, therefore, is that sPTH probably affects cardiac muscle contraction by at least two mechanisms, one of which involves non-adrenergic transmembrane calcium flux and the second β-adrenoceptors. 3. When these studies were extended into the clinical pharmacological field, it was found that plasma ultrafiltrates from severely hyperparathyroid patients in chronic renal failure inhibited like sPTH the cardiodepressant action of propranolol. No such effect was seen with ultrafiltrates from parathyroidectomized patients. Accordingly, high PTH levels may inhibit the action of cardiotropic drugs administered to hyperparathyroid patients, and may be one factor in the cardiomyopathy seen in such patients.     

Dissociation de deux composantes du comportement chez le rat sous l'effet de psychotropes

The staircase is a simple and rapid test and was used to study two components of exploratory behaviour in the rat. The scores of rearing and the number of steps climbed during three minutes were recorded.Various psychotropic drugs were tested, which modified these two parameters. Neuroleptic induced a parallel decrease of both, while benzodiazepines, meprobamate, amobarbitone and ethanol decreased the rearing at doses which left the steps climbed unchanged. At high doses, there was a parallel decrease of both parameters. Amphetamine, at lower doses, increased the rearing score alone.The comparison of the studied psychotropic drug effects with those of two muscle relaxants (by a comparison of the slopes of regression lines) suggests that either the observed benzodiazepine effects were only partly due to their myorelaxant action, or, that both myorelaxants have some anxiolytic action.The effect of amphetamine at low doses can be viewed as a demonstration of increased anxiety.

Ce travail a bénéficié d'une subvention de la Fondation pour la Recherche Médicale FranÇaise.     

The effects of pentobarbitone and urethane on pulmonary airway resistance in guinea-pigs and their interactions with drugs.

1 Propranolol increased pulmonary airway resistance (PAR) in the conscious guinea-pig, whereas atropine had no effect, suggesting the existence of a continual sympathetic bronchodilator tone. 2 The direct bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were modified by autonomic reflexes: a bronchodilator one, abolished by propranolol, and a cholinergic bronchoconstrictor one, seen with histamine. 3 Pentobarbitone increased PAR, an effect which was reduced by propranolol but which was unaffected by atropine. The bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were potentiated by pentobarbitone. 4 Pentobarbitone therefore appears to inhibit the adrenergic bronchodilator tone and to depress adrenergic reflexes, these being the preponderant autonomic influences in these experiments. 5 Like pentobarbitone, urethane increased PAR in the conscious guinea-pig and potentiated the bronchoconstrictor effects of the three amines. These actions are similarly attributed to a reduction in adrenergic influences.