Objective-Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation, including apoptosis. The present study was designed in dissecting the effects evoked by microparticles on vascular reactivity. Methods and Results-Microparticles from either apoptotic T lymphocytic cells or from plasma of diabetic patients with vascular complications induced vascular hyporeactivity in response to vasoconstrictor agents in mouse aorta. Hyporeactivity was reversed by nitric oxide (NO) synthase plus cyclooxygenase-2 inhibitors, and associated with an increased production of vasodilatory products such as NO and prostacyclin. Microparticles induced an upregulation of proinflammatory protein expressions, inducible NO-synthase and cyclooxygenase-2, mainly in the medial layer of the vessels as evidenced by immunochemical staining. In addition, microparticles evoke NF-B activation probably through the interaction with the Fas/Fas Ligand pathway. Finally, in vivo treatment of mice with lymphocyte-derived MPs induces vascular hyporeactivity, which was reversed by the combination of NO and cyclooxygenase-2 inhibitors. Conclusion-These data provide a rationale to explain the paracrine role of microparticles as vectors of transcellular exchange of message in promoting vascular dysfunction during inflammatory diseases. (Arterioscler Thromb Vasc Biol. 2005;25:2522-2527.)Key Words: Fas/Fas Ligand Ⅲ microvesicles Ⅲ proinflammatory proteins Ⅲ vascular dysfunction Ⅲ vasoactivity R ecent data suggest that inflammation play a central role in the origin and complications of cardiovascular disease. For instance, inflammation has a pivotal role in the development of atherosclerosis and the acute activation of the vascular wall with consecutive local thrombosis and altered vasoactivity. This process is orchestrated by the interactions between inflammatory cells, such as leukocytes and vascular cells, endothelial cells, and smooth muscle cells, which under activation or apoptosis, for example, lead to the release of circulating microparticles (MPs). MPs are vesicles shed from the blebbing plasma membrane of various cell types, such as platelets, T and B cells, monocytes, and endothelial cells during activation by agonists, shear stress, 1,2 or apoptosis. 3,4 MPs harbor cell surface proteins and contain cytoplasmic components of the original cell. They exhibit negatively charged phospholipids, chiefly phosphatidylserine, at their surface accounting for their procoagulant character 1 and proinflammatory properties. 5 Elevated levels of circulating MPs have been detected under pathological states, such as atherosclerosis, acute coronary syndrome, diabetes, preeclampsia, and sepsis. 4,6 -9 Furthermore, these pathologies are associated with vascular dysfunction including attenuation of endothelium-dependent vasodilatation, alteration of responsiveness of vascular smooth muscle to vasoconstrictor stimuli, or both. However, the mechanisms triggering the modifications of the vessel contraction/relaxati...

Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.

We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK2 and NK3 receptor agonists.

Arginine, initially classified as a non-essential amino acid, participates to multiple biological processes including release of several hormones, collagen synthesis during wound healing, antitumor and antibacterial activities and non-specific immunity. Nitric oxide synthase and arginase competes for L-arginine as a substrate and this event appears to play a key role in the regulation of the inflammatory process. In this framework recent studies have identified complex patterns of interactions among these enzymes. This review will emphasizes some effects of L-arginine on immune cell functions, including triggering of L-arginine-nitric oxide and arginase pathways, its biological properties and therapeutical applications.

No abstract