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Marrachelli V.G.,University of Angers | Marrachelli V.G.,French Institute of Health and Medical Research | Marrachelli V.G.,Hospital Clinico Universitario | Mastronardi M.L.,University of Angers | And 15 more authors.
PLoS ONE | Year: 2013

Microparticles are small fragments of the plasma membrane generated after cell stimulation. We recently showed that Sonic hedgehog (Shh) is present in microparticles generated from activated/apoptotic human T lymphocytes and corrects endothelial injury through nitric oxide (NO) release. This study investigates whether microparticles bearing Shh correct angiotensin II-induced hypertension and endothelial dysfunction in mice. Male Swiss mice were implanted with osmotic minipumps delivering angiotensin II (0.5 mg/kg/day) or NaCl (0.9%). Systolic blood pressure and heart rate were measured daily during 21 days. After 7 day of minipump implantation, mice received i.v. injections of microparticles (10 μg/ml) or i.p. Shh receptor antagonist cyclopamine (10 mg/kg/2 days) during one week. Angiotensin II induced a significant rise in systolic blood pressure without affecting heart rate. Microparticles reversed angiotensin II-induced hypertension, and cyclopamine prevented the effects of microparticles. Microparticles completely corrected the impairment of acetylcholine- and flow-induced relaxation in vessels from angiotensin II-infused mice. The improvement of endothelial function induced by microparticles was completely prevented by cyclopamine treatment. Moreover, microparticles alone did not modify NO and O2.- production in aorta, but significantly increased NO and reduced O2.- productions in aorta from angiotensin II-treated mice, and these effects were blocked by cyclopamine. Altogether, these results show that microparticles bearing Shh correct angiotensin II-induced hypertension and endothelial dysfunction in aorta through a mechanism associated with Shh-induced NO production and reduction of oxidative stress. These microparticles may represent a new therapeutic approach in cardiovascular diseases associated with decreased NO production. © 2013 Marrachelli et al.

Sarr F.B.,Laboratoire Of Physiologie Et Explorations Fonctionnelles | Sarr F.B.,Societes T University Bamako | Sarr M.,Laboratoire Of Physiologie Et Explorations Fonctionnelles | Sarr M.,Societes T University Bamako | And 14 more authors.
Journal of Medicinal Plants Research | Year: 2010

Scientific validation of pharmacological actions of 7 Senegalese plants used in traditional medicine for the treatment of respiratory illness was carried out. Changes in contractility of isolated rat trachea were assessed in organ chambers. Rings were allowed to equilibrate for 60 min before experiments were carried out, during which time the resting tension was adjusted, as required. Rings were first exposed to methanolic plants extracts (10 -2 and 10 -1 mg/ml) or solvent. After a 30 min incubation period, they were contracted with acetylcholine in a cumulative manner (10 -9 to 10 -3M). Extracts from leaves of Guiera senegalensis, Melaleuca leucodendron and Hymenocardia acida elicited a significant dose-dependant inhibition of the contractile agonist, suggesting further investigations on its chemical composition, the underlying mechanisms involved and its potential health value. However, in rings pre-incubated with extracts from Cymbopogon giganteus leaves and Salvadora persica roots, effect of the contractile agonist was not affected. Moreover, a hypereactivity was observed with extracts from Gossypium barbadense leaves and Cassia occidentalis seeds. These results provide evidence that Senegalese herbals may be of interest as valuable source of information for the selection of plants for focussed screening programmes and for therapeutically useful products. © 2010 Academic Journals.

Sarr M.,Laboratoire Of Physiologie Pharmaceutique | Sarr M.,Cheikh Anta Diop University | Sar F.B.,Laboratoire Of Physiologie Pharmaceutique | Sar F.B.,Cheikh Anta Diop University | And 7 more authors.
Cardiovascular Journal of Africa | Year: 2011

Aim: In endothelium-denuded arteries, the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) induced a persistent hypo-reactivity to vasoconstrictors, and low-molecular weight thiols such as N-acetyl cysteine (NAC) produced a relaxant effect. These effects were attributed to the formation of vascular NO stores. In arteries with a functional endothelium, such long-lasting effects on arterial tone have not been well characterised. In this study, we proposed to examine the possibility of storing exogenous NO when the vascular endothelium is still able to produce its own NO. Methods: For this purpose, changes in isometric tension of isolated arteries were assessed in organ chambers, and nitrosothiol formation was characterised by confocal microscopy. Results: In rat aortic rings with endothelium pre-exposed to GSNO, the contractile response to norepinephrine (NE) was not attenuated in comparison with control rings, but NAC induced a relaxant effect. However, an attenuation of the response to NE was observed in GSNO-exposed, intact aortic rings after inhibition of NO synthase by Nw-nitro-L-arginine methylester (L-NAME) or in GSNO-denuded rings. The relaxing effects of NAC were due to the mobilisation of NO from nitrosothiols after nitrosylation of protein SH residues. Moreover, the hypo-reactivity to NE and the relaxant effect of NAC were abolished by 1H-[1,2,4] oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, and partially by the K +-sensitive channel inhibitor tetra-ethyl-ammonium (TEA). Conclusion: These data show that endothelium-derived NO masked the persistent effect of GSNO in rat thoracic aorta. However, the ability of GSNO to form releasable NO stores without altering the vascular tone can be particularly useful in preventing endothelial dysfunction in which NO formation decreases.

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