H. Allain

Constriction of the Smooth Muscle of Rat Tail and Femoral Arteries and Dog Saphenous Vein Is Induced by Uridine Triphosphate via ‘Pyrimidinoceptors’, and by Adenosine Triphosphate via P2x Purinoceptors

Adenosine triphosphate (ATP) and uridine triphosphate (UTP) receptors were studied by comparing the contractile responses to UTP with those to ATP in the rat tail and femoral arteries and dog saphenous vein, after endothelium removal confirmed by histology, and near abolition of relaxation to acetylcholine. Contractions induced by ATP and UTP were dose dependent, as assessed from preparations at resting tension. Contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. In the rat tail artery and the dog saphenous vein, quinidine, nordihydroguaiaretic acid (NDGA) and phentolamine inhibited the contractions induced by ATP, whereas those induced by UTP were only slightly reduced in the presence of NDGA and were not antagonized by quinidine and phentolamine. In all three vessels, alpha-beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 was incapable of antagonizing contractions to ATP and UTP in these preparations. In addition, UTP-induced contractions were hardly inhibited in a calcium-free Krebs solution, whereas ATP was totally inhibited. We showed that a calcium antagonist, nicardipine, was more potent on the UTP-induced than on the ATP-induced contractions. These results showed the UTP-induced contraction to be mediated by a new class of receptors, qualified here as pyrimidinoceptors, for which no antagonist is known. These results were obtained in the tail and femoral arteries of the rat and from the dog saphenous vein. ATP induced contraction in these three vessels via P2x purinoceptors. P2x purinoceptors and pyrimidinoceptors are localized on the vascular smooth muscle.

Effect of triethyltin chloride on the central aminergic neurotransmitters and their metabolites: relationship with pathophysiology of aging.

Triethyltin (TET) salt intoxication provokes a myelinic vacuolisation associated with a white matter cerebral edema. The central nervous system disturbances accompanying these phenomena (Na-K-ATPase activity, neurological symptoms, water and sodium cerebral content) can be counteracted by drugs used in age-related brain failure; consequently, TET intoxication could be suggested as an experimental model for studying the aging process. The aim of the present study is to follow-up the biogenic amine concentrations in different brain areas of TET treated rats, knowing that modifications of cerebral amines exist throughout the aging process. The following results are obtained: the cerebral water content of the TET treated rats is significantly increased, confirming the existence of a brain edema. Monoamine concentrations are significantly decreased, specifically noradrenaline (in hypothalamus, mesencephalon, cerebellum); serotonin (in striatum, hypothalamus, mesencephalon); dopamine only in hypothalamus; these are accompanied by an increase of the metabolites 5 HIAA (in striatum and mesencephalon) and HVA (striatum). These modifications are compared to those occurring in physiological aging, and hypothetical mechanisms are reviewed. We conclude that TET intoxication must not be considered as a pathophysiological model of brain aging, but may be considered as a useful pharmacological tool for studying experimental drugs liable to counteract brain age-induced disturbances.

Anesthésie péridurale pour césarienne par association bupivacaïne-fentanyl

This prospective study was designed to evaluate the benefit of a bupivacaine-fentanyl mixture vs bupivacaine alone in epidural anaesthesia for caesarean section. In 10 women, 0.5% bupivacaine (1.18 ml per metamer) was injected in the epidural space. In 20 women, 0.5% bupivacaine (1.06 ml per metamer) was injected by the same route together with fentanyl (1.70 ± 0.09 g · kg−1). The bupivacaine-fentanyl group showed a significantly shortened onset of analgesia (p <0.001), as well as a significant reinforcement of this analgesia graduated from 0 to 4 (p <0.01 at 25 min, p <0.001 at 75 min and at the maximum of pain, for the two sets of scores). All the Apgar scores were maximal at 5 min. No clinical respiratory depression was observed in either the mothers or the neonates. Fetal and maternal blood concentrations were in favour of respiratory innocuousness of the method (peak fentanyl concentrations : in mothers 1.5 ng · ml−1, in neonates 0.8 ng · ml−1). Fentanyl never induced any significant haemodynamic variations. Pruritus and nausea respectively occurred in six and two patients respectively in the bupivacaine-fentanyl group. In conclusion, in caesarean section, the adjunction of fentanyl to bupivacaine significantly improved analgesia without any clinical respiratory depression both in the mother and the neonate.

L-type voltage-dependent calcium channels do not modulate aminergic neurotransmitter release induced by transient global cerebral ischaemia: an in vivo microdialysis study in rat

Cerebral ischaemia induces considerable neurotransmitter exocytosis, mediated by calcium entry in neurones, essentially via the N-type, voltage-dependent channels, which are insensitive to calcium blockers. Nonetheless, these blockers, by unclear mechanisms, exert a neuroprotective effect when used in experimental ischaemic models. On the other hand, the existence of L-type, voltage-dependent channels, the only ones responding to the action of calcium blockers on synapses, argues in favour of their possible concomitant action in certain highly pathological situations. We studied the action of three calcium blockers, nimodipine, diltiazem and verapamil (administered at a concentration of 100 μM directly into the striatum of rats), on the extracellular release of dopamine and serotonin, and on the level of their main metabolites, in a model of transient global cerebral ischaemia (four-vessel occlusion). The total absence of effect of these molecules on neurotransmitter release induced by ischaemia proves the non-involvement of this mechanism in the protective action of calcium entry blockers on ischaemic lesions, and the absence or very weak action of L-type, voltage-dependent presynaptic channels in the striatum of rats.

Temporal profile of aminergic neurotransmitter release in striatal dialysates in rats with post-ischemic seizures.

The temporal profiles of aminergic neurotransmitter levels and of their acid metabolites after transient global cerebral ischemia in awake rats with and without subsequent seizures were compared using a microdialysis approach. In seizure animals, the post-ischemic levels of dopamine and serotonin were higher than the levels observed in the non-seizure controls. Inversely, the levels of the three neurotransmitter metabolites increased rapidly in the controls but not in seizure animals, where they remained at the low levels observed during and immediately after ischemia. This particular pattern is similar to that observed in rats submitted to prolonged ischemia or pretreated with monoamine oxidase inhibitors. In the seizure animals, neurotransmitter metabolites remained at low levels, as if the hypoxia had continued after the period of ischemia, inhibiting monoamine oxidase activity and, perhaps, neurotransmitter recapture.

Analgésie péridurale au cours du travail : comparaison de trois associations fentanyl-bupivacaïne et de la bupivacaïne seule

Resume Les auteurs rapportent un essai controle organise en simple aveugle, portant sur 159 primipares reparties de facon equilibree en quatre groupes. Dans chaque protocole, linjection peridurale initiale de la solution anesthesique est de 10 ml, les reinjections de 6 ml. La solution anesthesique comprend soit de la bupivacaine a 0,25 % seule, soit une association bupivacaine a 0,25 % et fentanyl a des doses de 0,05 mg (protocole II), 0,1 mg (protocole III) et 0,15 mg (protocole IV) pour 10 ml de la solution. Les parturientes du protocole II beneficient de la meilleure analgesie (delai dinstallation plus court, qualite tres satisfaisante, action suffisamment durable). Dans ce protocole, la duree du travail est la plus courte. Lexpulsion seffectue normalement, le score dApgar des nouveau-nes est de 10 a 10 min. Aucune depression respiratoire clinique nest retrouvee aussi bien chez la mere que chez le nouveau-ne. Un prurit localise imputable au fentanyl apparait chez 20 % des parturientes. Les fortes doses de fentanyl (protocoles III et IV) nameliorent pas les parametres analgesiques et saccompagnent dune augmentation du nombre dextractions instrumentales et de cesariennes. Lanalgesie correcte chez 97 % des femmes du protocole II permet devoquer une occupation complete des recepteurs opiaces pour les segments concernes par les douleurs du travail obstetrical.

The use of bromocriptine for testing central dopaminergic reactivity.

A single oral intake of 10 mg of Bromocriptine can modify both plasma renin activity (PRA) and arterial blood pressure (BP). The changes in both variables depend on the integrity of the central dopaminergic systems. The parkinsonians whose extrapyramidal symptoms are markedly improved by l-Dopa in association with a decarboxylase inhibitor (IDC) and the untreated parkinsonians are the only patients whose PRA and BP are lowered 1 h after Bromocriptine ingestion. The results obtained in the l-dopainduced dyskinetic parkinsonians are similar to those obtained in the group of l-Dopa-resistant patients. This points to the paradoxical hypothesis of dopaminergic hyposensitivity in the dyskinetic patients.In spite of the absence of correlation between PRA and BP, it is possible that lowering of BP by Bromocriptine is linked to the parallel decrease of PRA. An increase of the BP may be obtained in the dyskinetic and l-Dopa-resistant groups. These data point to a possible involvement of central dopaminergic systems in some aspects of hypertension.

L'action centrale des antagonistes calciques

Resume Primitivement reserves aux affections cardio-vasculaires, les antagonistes calciques voient leur champ dapplication selargir vers la pathologie du systeme nerveux central. Ils ne representent pas une classe pharmacologique homogene. Pour certains dentre eux le passage de la barriere hemo-encephalique a pu etre demontre et lexistence de sites specifiques de liaison pour les inhibiteurs calciques au niveau du tissu cerebral, chez lanimal comme chez lhomme, est bien etablie. Le role primordial du Ca++ et de son accumulation intraneuronale dans les processus de liberation des neurotransmetteurs dans la synapse, dans le declenchement de la cascade arachidonique et ses consequences deleteres et finalement dans la necrose et la mort cellulaire, rendait logique la recherche dune protection par les inhibiteurs calciques dans les phenomenes physiopathologiques concernes. En pharmacologie experimentale, ces molecules ont ete testees avec succes sur des modeles dischemie et dhypoxie, sur le vasospasme, les convulsions, la douleur et dans des tests neuro- et psychopharmacologiques. En pharmacologie clinique, des resultats encourageants ont ete obtenus dans le traitement de la pathologie vasculaire cerebrale mais egalement dans lepilepsie et peutetre meme dans certaines formes de psychoses.

Impairment of acquired temporal response regulation of rats under normobaric hypoxia

Effects of hypoxia on learning involving temporal regulation of behaviour was investigated. Under 10% hypoxia there was a decrease in the number of conditioned responses, and the efficiency of reinforcement, but no modification of temporal discrimination. Normobaric hypoxia may be a useful model for studying certain behavioural and pharmacological effects of cerebral circulatory insufficiency, and their implications at the level of the central nervous system, but it would be incorrect to use such a model to study factors that might prevent the loss of acquired knowledge.

Plasmatic renin activity in patients treated with L-dopa and inhibitor of dopa decarboxylase (IDC).

Plasmatic renin activity (PRA) was studied in patients receiving l-dopa, together with a decarboxylase inhibitor, at rest times and after periods of physical exertion. Although we can superimpose the results from untreated Parkinsons disease patients on those of the control group, the results are inversed in stabilized patients (lowered PRA) and dyskinetic patients (increased PRA). There is a definite correlation between the increase in PRA and intensity of the dyskinesia. Dosage is the only other factor differentiating the two groups of Parkinsonians treated. The figures relative to arterial pressure are studied in the various groups.