4. Endothelin, one of the most potent vasoconstrictors Was first discovered by Yanagisawa and co-workers in 1988….. (Yanagisawa M, Kurihara H, Kimura S et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332: 411-5 .) It was first isolated, characterised, and cloned in porcine aortic endothelial cells
11. NO diffuses to smooth muscle cells and initiates (cGMP) by activating soluble cytosolic guanylyl cyclase. Elevation of cGMP levels causes vasodilation by decreasing intracellular calcium in smooth muscle cells Activation of ETA receptors results in calcium influx via phospholipase C (PLC) mediated diacylglycerol (DAG) and inositol trisphosphate (IP3) production. DAG activates protein kinase C (PKC), which, alongside increased intracellular calcium, causes phosphorylation of myosin kinase and smooth muscle cell contraction .
24. Role Of Endothelin Antagonism in Kidney diseases Given the role of Endothelins in several processes that lead to progression of chronic kidney disease, the possibility that Endothelin antagonism may be beneficial has been studied
25. Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade . Goddard, J, Johnston, NR, Hand, MF, et al. Circulation 2004; 109:1186.
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29. ASCENT Trial Avosentan on Doubling of Serum Creatinine, End Stage Renal Disease and Death in Diabetic Nephropathy
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31. Health Authority: Bulgaria: Bulgarian Drug Agency; Canada: Health Canada; China: State Food and Drug Administration; Columbia: Republica de Colombia, Ministerio de la Proteccion Social; Croatia:Ministry of Health; Czech Republic: State Institute for Drug Control; Estonia: The State Agency of Medicine; Finland: National Agency for Medicines; Germany: Federal Institute for Drugs and Medical Devices; Hungary: National Institute of Pharmacy; India: The Drugs Controller General; Indonesia: Badan Pom (NA-DFC); Italy: Ministry of Health; Israel: The Ministry of Health, Pharmaceutical Department; Korea: Korea Food and Drug Administration; Latvia: State Agency of Medicines; Lithuania: State Medicine Control Agency - : National Pharmaceutical Bureau Control; Mexico: Federal Commission for Protection against Health Hazards; Peru: Instituto Nacional de Salud; Philippines: Bureau of Food and Drugs; Poland: Ministry of Health; Romania: State Institute for Drug Control; Russia: Federal Services for Supervision in the area of Healthcare and Social Development; Singapore: Health Sciences Authority; Slovakia: State Institute for Drug Control; South Africa: Medicines Control Council; Spain: Agencia del Medicamento y Productos Sanitaros; Sweden: Medical Products Agency; Thailand: Ministry of Publich Health; Head of Thai Drug Control Division; Taiwan: Bureau of Pharmaceutical, Department of Health; Turkey: Ministry of Health; United Kingdom: Medicines and Healthcare Products Regulatory Agency; United States: Food and Drug Administration Ministry of Health; Malaysia
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33. Role of ET-A receptor antagonism in Heart Failure Love MP, Haynes WG, Gary GA et al. Vasodilator effects of endothelin-converting enzyme inhibition and ET-A receptor blockade in chronic heart failure patients treated with ACE inhibitors. Circulation 1996; 94: 2131-7.
