Bernard Saïag

Uptake and Flow-induced Release of Uridine Nucleotides from Isolated Vascular Endothelial Cells

Endothelial cells were isolated from rabbit thoracic aorta and cultured. Uptake of radioactivity was studied during incubation with 3H-uridine and 3H-uridine triphosphate (3H-UTP). After incubation with 3H-uridine and analysis by thin layer chromatography, the pyrimidines detected in the cell cytoplasm were 3H-UTP (30.8 ± 0.9%), 3H-UDP (uridine diphosphate, 4.3 • 2.1%). 3H-UMP (uridine monophosphate, 53.6 ± 1.1%) and 3H-uridine (7.1 3 0.9%). After incubation with H-UTP, there was also an uptake of radioactivity which was inhibited at low temperature (89.9 ± 6.1% at 4 °C), by dipyridamole (89.0 ± 7.1%) and N-ethylmaleimide (79.2 • 4.3%). The pyrimidines detected were 3H-UTP (24.7 • 3%), 3H-UDP (4.6 ± l%), 3H-UMP (35 ± 3.7%) and 3H-uridine (18.4 • 5%). Cultured endothelial cells were incubated with 3H-UTP or 3H-uridine and 3H-uridine for 90 min. These cells were perfused (0.5 ml/min) then stimulated twice by increased flow (3.0 ml/min) in order to compare their ability to release UTP and its derivatives. UT...

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.

Mechanistic Basis for the Development of Anti-Ischemic Drugs

The pharmacology of cerebral ischemia features 100 molecules and 20 potentially interesting mechanisms for preventing the tissue damage induced by anoxia-ischemia. The intricacy and complexity of the

Effects of an Acute Exercise on Endothelium Function in Athletics YoungSubjects: A Case Control Study

Aim: to investigate vascular reactivity on forearm skin blood flow (FSBF) in response to iontophoresis of acetylcholine (ACh) after an acute exercise. Materials and method: 49 healthy male subjects 29 trained and 20 sedentary (recruited according to their oxygen consumption) participated in this case control study (mean age: 15 ± 1 year). Incremental exercise testing was performed by means of an individualized and personalized exercise test protocol. FSBF was measured before and after exercise using a laser Doppler flowmeter in response to local iontophoresis of a cumulative dose of ACh. Results: Although groups were not different in age, height or body mass index, weight, resting heart rate, maximum oxygen consumption was significantly different (sedentary 40.05 ± 4.53 and trained 51.65 ± 5.76 ml.min-1. kg-1) (p<0.05; p<0.001; p<0.001, respectively). The mean response of FSBF to ACh was significantly increased after incremental exercise in the two groups (349%). Maximal FSBF response to ACh was significantly greater in trained (987% ± 78) than in sedentary (638% ± 42) (p=0.001) after a single acute exercise. Conclusion: Response of FSBF to ACh-induced endothelium dependent relaxation was affected by the level of training whether before or after an acute exercise.