Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. The goal of this study was to investigate the effects of dual ET receptor antagonism in the early phase (2 months) and in the late phase (5 months) of diabetic nephropathy in rats, and to compare this approach to angiotensin-converting enzyme inhibition. Four groups of uninephrectomized streptozotocin-induced diabetic rats were assigned to receive orally vehicle, bosentan, enalapril, or their combination. A fifth group consisted of nondiabetic, uninephrectomized rats. At 2 weeks, untreated diabetic rats exhibited increased glomerular filtration rate and renal plasma flow. Bosentan, enalapril, and the combination all prevented hyperfiltration and hyperperfusion. By 5 months, diabetic rats developed marked increases in mean arterial pressure and renal vascular resistance, progressive proteinuria, and renal structural damage with glomerular sclerosis and hypertrophy. Bosentan completely prevented the development of hypertension and renal vasoconstriction, and largely prevented the development of proteinuria and renal structural injury. The renal protective effect of bosentan was comparable to that of enalapril or the combination, although its anti-proteinuric effect was less. Clinical studies are warranted to assess whether ET receptor antagonism can have additive effects on top of ACE inhibition, the current treatment of choice in diabetic nephropathy.
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PMID:Chronic endothelin receptor blockade prevents both early hyperfiltration and late overt diabetic nephropathy in the rat. 1282 26

The endothelin axis, recognized for its vasoconstrictive action, plays a central role in the pathology of pulmonary arterial hypertension (PAH). Treatment with approved endothelin receptor antagonists (ERAs), such as bosentan, ambrisentan, or macitentan, slow down PAH progression and relieves symptoms. Several findings have indicated that endothelin is further involved in the pathogenesis of certain other diseases, making ERAs potentially beneficial in the treatment of various conditions. In addition to PAH, this review summarizes the use and perspectives of ERAs in cancer, renal disease, fibrotic disorders, systemic scleroderma, vasospasm, and pain management. Bosentan has proven to be effective in systemic sclerosis PAH and in decreasing the development of vasospasm-related digital ulcers. The selective ERA clazosentan has been shown to be effective in preventing cerebral vasospasm and delaying ischemic neurological deficits and new infarcts. Furthermore, in the SONAR (Study Of Diabetic Nephropathy With Atrasentan) trial, the selective ERA atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease. These data suggest atrasentan as a new therapy in the treatment of diabetic nephropathy and possibly other renal diseases. Preclinical studies regarding heart failure, cancer, and fibrotic diseases have demonstrated promising effects, but clinical trials have not yet produced measurable results. Nevertheless, the potential benefits of ERAs may not be fully realized.
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PMID:Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy. 3219 49