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Les proprietes sedatives et anxiolytiques du principe psychoactif principal du cannabis, le delta-9 tetrahydrocannabinol (THC), sont connues depuis des millenaires. Cette connaissance empirique a ete confirmee ces dernieres annees par une meilleure comprehension des mecanismes d'action du THC. Au niveau neuronal, il induit une diminution intracellulaire du potassium et une augmentation du calcium. Ceci se traduit par une alteration des capacites d'exocytose de certains neurotransmetteurs, dont le glutamate. Par ailleurs, il est desormais bien etabli que les zones du cerveau dans lesquelles le THC exerce ces effets sont les memes que celles ou agissent les medicaments sedatifs et les betabloquants, substances egalement utilisees dans la pratique du dopage. Les proprietes sedatives du cannabis sont recherchees par les athletes, les jours precedant les competitions pour favoriser l'endormissement, un souci majeur pour ces sportifs de haut niveau. Dans les disciplines sportives necessitant un etat de relaxation important au cours de la competition, ce qui est le cas pour tous les sports d'adresse (tir, equitation, etc.), les proprietes anxiolytiques du cannabis sont egalement tres attractives. En consequence, et bien que le cannabis puisse etre responsable d'une diminution des performances biomecaniques, il est utilise par les sportifs de haut niveau pour son aptitude a ameliorer les performances psychologiques ; il est donc logique qu'il soit proscrit au meme titre que certaines classes de medicaments destines a se substituer aux methodes naturelles de preparation psychologique.

The aim of this study was to develop a technique that could serve as an index of portosystemic shunt (PSS) blood flow in portal hypertensive rats whose main shunt is the splenorenal shunt (SRS). The main hemodynamic measurements performed were: SRS blood flow by the transit-time ultrasound (TTU) method, percentage of PSS, and regional blood flows by the microsphere method. We determined the accuracy and reproducibility of SRS blood flow measurements under baseline and pharmacological (octreotide) conditions. SRS blood flow was compared with other hemodynamic characteristics. Two models of portal hypertension were used: secondary biliary and dimethylnitrosamine cirrhosis. The SRS blood flow was correlated with mesenteric (r = .76; P < .001) and splenic (r = .67; P < .01) PSS percentages. The intra- and interobserver agreements for SRS blood flow were excellent: ric = .99 and ric = .98, respectively. SRS blood flow was six times higher in portal hypertensive rats (0.6 ± 0.7 mL · min−1 · 100 g−1) than in sham rats (0.1 ± 0.1 mL · min−1 · 100 g−1 [P < .01]). Octreotide significantly decreased SRS blood flow but not mesenteric or splenic PSS percentages. SRS is the main PSS in rats. The measurement of SRS blood flow by TTU is accurate and reproducible. This method can be used to identify new mechanisms in hemodynamic studies that differ from those identified by the measurement of the percentage of PSS by the microsphere method, especially in pharmacological studies.

Cocaine abuse can cause cardiovascular damage leading to hypertension, myocardial ischaemia and infarction. This might be partly due to the effects of cocaine on the microcirculation about which little is known, although its effects on the macrovessels are well documented. Accordingly, we used in vivo videomicroscopy to study the vasoconstrictive effect of cocaine on arterioles of different diameter. They were classified into three orders (A2, A3, A4) according to their position in the microvascular network and their diameter. Since calcium antagonists have been reported to exert a protective effect against the cardiovascular disorders induced by cocaine, we tested the hypothesis that this protective action occurs in the microcirculation. We found that intra-arterial administration of the calcium antagonist Nitrendipine greatly inhibited the vasoconstriction induced by cocaine in all three arteriole orders. The degree of inhibition ranged from 44 to 56%. Combined administration of benzodiazepine and an angiotensin converting enzyme inhibitor has also been reported to protect rats against cocaine-induced hypertension and to increase survival rates after a toxic dose of cocaine. Since the mechanisms of this protection are not yet clear, we also studied the effect of the angiotensin converting enzyme inhibitor Enalaprilat on cocaine-induced vasoconstriction. Intra-arterial administration of Enalaprilat inhibited this vasoconstriction slightly but significantly in arteriole orders 2 and 3 by 27 and 24% respectively, but not in order 4. We concluded that Nitrendipine is a powerful inhibitor of cocaine-induced vasoconstriction in the microcirculation. The small but significant inhibition found with Enalaprilat for the larger arterioles suggests that the local angiotensin II level may affect the response to cocaine. However, since the Enalaprilat-induced inhibition was very limited, we conclude that mechanisms other than those occurring in the peripheral microcirculation account for the protection afforded by Enalaprilat against the harmful effects of cocaine.

Background/Aims: The action sites and kinetic effects of octreotide and terlipressin may be different. Therefore, we studied the hemodynamic effects of acute administration of these drugs alone or in combination in rats with portal hypertension due to portal vein ligation. Methods: In a first study performed in anesthetized rats, hemodynamics were measured before and after drug administration (placebo, octreotide: 8 μg·kg −1 ·h −1 for 30 min, terlipressin: 50 μg/kg bolus, terlipressin + octreotide at the same doses). The second study, performed in conscious rats, included the same groups and drug doses; hemodynamics were measured every 10 min for 1 h. The third study tested the effect of preinfusion of octreotide on responsiveneness to terlipressin. Results: Terlipressin produced more marked systemic effects than octreotide by decreasing heart rate and cardiac output and increasing mean arterial pressure. Terlipressin produced a greater decrease in portal pressure than octreotide: placebo: −3±5%, terlipressin: −42±8%, octreotide: −16±10%, combination: −44±8% (conscious rats at 20 min, p −4 ). The decrease in portal pressure was immediate and lasted at least 60 min with both drugs. Octreotide significantly decreased spleno-renal shunt blood flow (% variation): placebo: −6±8, terlipressin: −15.5±20, octreotide: −22.5±20, combination: −27±10 ( p −2 ). Octreotide preinfusion significantly increased the responsiveness of arterial pressure and heart rate to terlipressin. Conclusions: Terlipressin decreases portal pressure significantly more than octreotide, while only octreotide significantly decreases collateral blood flow. Simultaneous administration of these drugs does not have significant additive effects but has complementary effects. The preadministration of octreotide alters systemic reponse to terlipressin.

Oldendorf's method has been widely used to estimate and characterize the transport of amino acids across the blood-brain barrier in rats. However, it cannot be used with very young animals. A modification of this method (retrograde injection into the right brachial artery, instead of orthograde injection into the common carotid artery) allowed the estimation of the brain uptake index of some amino acids in 5-, 12- and 19-day-old rats, as well as the study of self- and cross-inhibition and of sodium dependency. The results obtained showed that the pattern of transport of amino acids was different in 5-day-old and in 19-day-old rats. In young rats, besides the presence of the L-system, which transported large neutral amino acids as in adult rats, the presence of another system of transport for neutral amino acids was strongly suggested. The activity of this system which transported alanine, serine, cysteine and threonine, decreased during development and it had many of the characteristics of the ASC system described by Christensen7. In addition, the presence of a system of transport for β-amino acids at the blood brain barrier is suggested.

The physiological consequences of lowering blood affinity are still contradictory. With modest P50 increases, it is often difficult to evidence these effects. In another hand a difficulty to analyse the observed result is induced by the side effects due to the manipulations of the blood in order to increase the P50. Rightwards shifts of the O2 dissociation curve (ODC), obtained in lysed and resealed erythrocytes following encapsulation of inositol hexaphosphate (IHP), were recently described by Teisseire et al.11. This procedure led to very large increase in P50 and the goal of this study was to assess the effects of large decrease of hemoglobin affinity on coronary blood flow in blood perfused isolated rat heart.

The aim of this study was to validate a new technique for the measurement of cardiac output (CO) based on ultrasound and dilution (COUD) in anesthetized rats. A transit time ultrasound (TTU) probe was placed around the rat carotid artery, and ultrasound velocity dilution curves were generated on intravenous injections of saline. CO by COUD were calculated from the dilution curves for normal and portal hypertensive rats in which CO was known to be increased. COUD was compared with the radiolabeled microsphere method and with direct aortic TTU flowmetry for baseline CO and drug-induced CO variations. CO in direct aortic TTU flowmetry was the ascending aorta blood flow measured directly by TTU probe (normal use of TTU flowmetry). The reproducibility of COUD within the same animal was also determined under baseline conditions. COUD detected the known CO increase in portal hypertensive rats compared with normal rats. CO values by COUD were correlated with those provided by microsphere technique or direct aortic TTU flowmetry (adjusted r = 0.76, P < 10−4 and r = 0.79, P < 0.05, respectively). Baseline CO values and terlipressin-induced CO variations were detected by COUD and the other techniques. Intra- and interobserver agreements for COUD were excellent (intraclass r = 0.99 and 0.98, respectively). COUD was reproducible at least 10 times in 20 min. COUD is an accurate and reproducible method providing low-cost, repetitive CO measurements without open-chest surgery. It can be used in rats as an alternative to the microsphere method and to direct aortic flowmetry.