Biomedical subjects

Vincent Richard

Publications and source records attributed to Vincent Richard.

24 records · Page 2Linked to original sources

PubMed2002

Endothelial protective effects of preconditioning.

The consequences of cardiac ischemia-reperfusion are not limited to myocytes but also extend to the coronary endothelium, where they are characterized by decreased nitric oxide (NO)-dependent relaxations. Given the essential role of the endothelium and NO in the regulation of vascular tone as well as platelet and leukocyte function, protection of coronary endothelial cells is an important therapeutic target. In this context, several studies have shown that both early and delayed preconditioning may prevent endothelial dysfunction after index ischemia-reperfusion. This endothelial protection most likely results from the inhibitory effects of preconditioning on expression of endothelial adhesion molecules, resulting in reduced neutrophil-endothelial interactions. The mechanisms of early endothelial preconditioning resemble those described at the level of the myocytes, and may involve mediators such as adenosine, bradykinin, NO and free radicals, together with activation of protein kinase C and opening of ATP-sensitive potassium channels. With regard to delayed preconditioning, recent studies have shown that both NO and free radicals are involved as triggers of this second window of endothelial protection. The complex interactions between these two radical species ultimately lead to a delayed increase in NO production, most likely responsible for the decreased adhesion of neutrophils to endothelial cells. Further identification of the triggers and mediators of this endothelial protection will allow the development of new therapeutic agents targeting both the myocardium and the coronary vasculature.

Adenosine↗

PubMed2002

Peroxynitrite triggers a delayed resistance of coronary endothelial cells against ischemia-reperfusion injury.

Experiments were designed to test whether nitric oxide (NO) and peroxynitrite trigger delayed coronary endothelial protection induced by preconditioning (PC) in rats. Prolonged ischemia reperfusion markedly reduced the response of isolated coronary arteries to acetylcholine, and this was prevented by PC performed 24 h earlier. The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) administered during PC abolished its delayed endothelial protective effect, whereas the inducible NOS inhibitor N-(3(aminomethyl)benzyl)acetaminide had no effect. Delayed endothelial PC was also abolished by the peroxynitrite scavengers selenomethionine or uric acid given during PC. In parallel, the NO/peroxynitrite donor S-morpholinosydnonimine and authentic peroxynitrite, administered 24 h before prolonged ischemia-reperfusion mimicked endothelial PC, whereas the NO donor S-nitroso-N-acetylpencillamine had no effect. This suggests that peroxynitrite is an essential trigger of the delayed coronary endothelial protection induced by PC in rat hearts.

Acetylcholine↗

PubMed2002

Tissue Doppler imaging differentiates physiological from pathological pressure-overload left ventricular hypertrophy in rats.

BACKGROUND: The myocardial velocity gradient (MVG) is a recent index of regional myocardial function derived from endocardial and epicardial velocities obtained by tissue Doppler imaging (TDI). This index might be useful for discriminating between physiological and pathological left ventricular hypertrophy (LVH) and for documenting the early transition from compensated LVH to heart failure. We sought to compare MVG measured across the left ventricular posterior wall between normal rats and rats with physiological (exercise) and pathological (pressure-overload) LVH. METHODS AND RESULTS: Wistar rats were assigned to one of the following groups: sedentary, exercise (swimming), and 2-month or 9-month abdominal aortic banding. Compared with sedentary rats, exercise and 2-month banding led to similar and significant LVH. After 2-month banding, conventional parameters of systolic function (left ventricular fractional shortening and dP/dt(max)) were not affected. However, systolic and diastolic MVG were similar in exercise and sedentary rats but were significantly lower in rats with aortic banding. Aortic debanding after 2 months led to a full recovery of MVG, whereas MVG remained decreased when debanding was performed after 9 months. CONCLUSIONS: Myocardial contraction and relaxation assessed by TDI were impaired in pressure-overload LVH but not in exercise LVH. Therefore, TDI is more sensitive than conventional echocardiography for assessing myocardial dysfunction in pressure-overload LVH and for predicting early recovery in myocardial function after loading conditions normalization.

Animals↗

PubMed2002

Heat stress increases endothelium-dependent relaxations and prevents reperfusion-induced endothelial dysfunction.

1. Heat stress has been widely used to stimulate the expression of stress proteins and is associated with various cardiovascular changes, including anti-ischaemic effects. However, the effect of heat stress on endothelial function is less clear. 2. Heat stress was induced in anaesthetized rats by increasing body temperature to 42 degrees C for 15 min. Twenty-four hours later, segments of rat aorta and mesenteric and coronary arteries were mounted in organ chambers. 3. Heat stress markedly increased relaxation to acetylcholine (ACh) in all three blood vessels studied, without affecting the response to the nitric oxide (NO) donor sydnonimine-1. 4. Heat stress also increased aortic relaxation to histamine and the calcium ionophore A23187. 5. In the aorta, an inhibitor of NO synthesis abolished the response to ACh in both control and heat stressed-rings, whereas a cyclo-oxygenase inhibitor had no effect. 6. Heat stress also prevented completely the impaired response to ACh in coronary arteries isolated from rats subjected to myocardial ischaemia and reperfusion. 7. Thus, heat stress increases the stimulated release of NO the rat aorta and mesenteric and coronary arteries and prevents reperfusion-induced injury at the level of the coronary endothelium.

Animals↗

PubMed2002

Alpha2-adrenoceptor ligands inhibit alpha1-adrenoceptor-mediated contraction of isolated rat arteries.

The experiments in this study were designed to investigate the potential relaxing effects of different compounds known as alpha2-imidazoline ligands (either agonists or antagonists) in isolated rat arteries, and to test the role of nitric oxide (NO) and prostaglandins, in addition to the influence of the nature of the contracting agent in these responses. Segments of mesenteric arteries were isolated and mounted in a small vessel myograph (JP Trading, Aarhus, Denmark) for isometric tension recording, while segments of gracilis muscle arteries were cannulated and studied in the pressurized state using an arteriograph (Living Systems Instrumentation, Burlington, VT, USA). In phenylephrine precontracted mesenteric arteries, the agonists clonidine, BHT920, UK 14304, and rilmenidine, as well as the antagonists idazoxan, yohimbine and rauwolscine, all induced marked relaxations. Similarly, clonidine and idazoxan, both induced marked dilatations of phenylephrine preconstricted gracilis muscle arteries. In both mesenteric and gracilis muscle arteries, the responses to clonidine and idazoxan were not affected by the NO synthase inhibitor (omega)-nitro-L-arginine (L-NA, 10(-5) M) or the cyclooxygenase inhibitor diclofenac (10(-5) M). In mesenteric arteries, the responses to clonidine or idazoxan were similar when the arteries were precontracted by different alpha1-adrenoceptor agonists (phenylephrine, methoxamine or norepinephrine). In contrast, in arteries precontracted by PGF2alpha or endothelin, clonidine induced contractions while idazoxan induced very modest relaxations. Thus, alpha2-adrenoceptor/imidazoline ligands (whether agonists and antagonists) induce paradoxical relaxation of small mesenteric or gracilis muscle arteries of rats, which are not affected by NO-synthase or cyclooxygenase inhibition, and appear related to direct non specific interactions of the alpha2-imidazoline ligands with alpha1-adrenergic receptors in vascular smooth muscle.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2002

Intestinal preconditioning prevents systemic inflammatory response in hemorrhagic shock. Role of HO-1.

Intestinal ischemia-reperfusion has been implicated in the systemic inflammatory response and organ injury in hemorrhagic shock, but the exact role of the intestine has never been directly demonstrated. Preconditioning (PC) with brief periods of intermittent ischemia is a known potent anti-ischemic intervention and thus can be used as a tool to assess the role of local intestinal ischemia-reperfusion injury in systemic inflammatory response. Thus rats were first subjected to sham surgery or intestinal preconditioning with four cycles of 1-min ischemia and 10 min of reperfusion 24 h before hemorrhagic shock followed by resuscitation. PC reduced fluid requirements, lung edema, and lactate and tumor necrosis factor-alpha production. These effects were abolished by the heme-oxygenase-1 (HO-1) inhibitor tin protoporphyrin (Sn-PP). PC induced more than fivefold in intestinal HO-1 expression. These results suggest that intestinal ischemia-reperfusion is a major trigger for inflammatory response and organ injury in nonseptic shock. HO-1 appears to play an important role in the protective effect of intestinal preconditioning.

Animals↗