Introduction: Forefronts in Endothelin / Introduction : Progrès des conaissances sur l'endothéline

摘要

Forefronts in EndothelinnThe 10th International Conference on Endothelin (ET-10)nwas held in Bergamo, Italy, 16–19 September 2007, undernthe auspices of the Mario Negri Institute for PharmacologicalnResearch. The meeting, attended by approximately 230 scientistsnfrom academia and industry, was part of a series of biennialnconferences that rotate between North America, Europe,nand Asia. Data were presented from studies that addressednthe role of ET in health and disease involving a wide range ofnorgan systems.nThe manuscripts selected for publication in two issues ofnthe Canadian Journal of Physiology and Pharmacology illustratensome of the achievements presented at ET-10. The issuenof receptor dimerization was discussed; this could shednlight on the paradoxical effect of decreased natriuresis observednin ETA knockout animals. The role of ET-2 was highlightednin physiologic processes spanning oocyte maturation,nthermoregulation, lung development and nutrition, as well asnin pathologic processes such as retinal degeneration and inflammatorynbowel disease. The pivotal role of ET in control ofnbasal renal–cardiovascular function and in disease conditionsnof abnormal vascular tone was discussed. Recent data on thenuse of ET antagonists in humans in pulmonary arterial hypertensionnare conclusive and very encouraging, but further carefullyndesigned studies are needed in other diseases. Clinicalntrials on ET antagonists in kidney disease, and particularly inndiabetic nephropathy, are needed. A new paradigm for cancerntherapy addressed the use of selective ET antagonists thatnblock tumor and (or) stromal cells; this represents a fertilenarea for new studies aimed at interfering both with the growthnof primary tumors and with metastasis. Another importantnarea of application of ET antagonists is neuropathic inflammatorynand neoplastic pain. The ongoing clinical trials in metastaticncancer represent an opportunity to evaluate the efficacynof ET blockers in reducing metastasis and pain. Finally,nemerging targets for exploration of the pathologic role of ETninclude traumatic brain injury, acute lung injury, sickle cellnanemia, and inflammatory bowel disease.