| description: |
In uremia, the renin-angiotensin-aldosterone system (RAAS) and the endothelin (ET)-1 systems are activated. Therapeutic management of diseases in which activity of the RAAS known to be increased has been greatly facilitated by the availability of classes of drugs that inhibit angiotensin-converting enzyme or block Ang-II receptors. Experimental and clinical studies using these renoprotective drugs indicate that RAAS blockers also slow the pace of progressive renal injury resulting from kidney diseases of diverse etiologies. We have shown recently during our previous work supported by the Estonian Science Foundation grant 3959 and 5493 that RAAS blocker, Ang-II type-1 receptor antagonist (AT1RA) losartan, modulated beneficially the oxidative status in the remnant kidney. These studies helped Dr. Pechter ja Dr.(vet) Aunapuu to do their doctoral thesis in 2004. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilatation, a proinflammatory state, and prothrombotic properties. Production of ET-1 is increased in the endothelium and the kidney in salt-dependent models of hypertension. ET-1 elicits an inflammatory response by increasing oxidant stress in the vascular wall, which induces vascular remodeling and endothelial dysfunction found in the hypertensive models that exhibit an endothelin-mediated component. Endothelin receptor antagonism reduces blood pressure and vascular hypertrophic remodeling present in these hypertensive models. Endothelin receptor antagonists lower blood pressure in hypertensive patients. They could become therapeutic agents for prevention of target organ damage in hypertension and in type 2 diabetes, chronic renal failure and congestive heart failure. Current work designed to to clarify whether angiotensin or ET receptor antagonists inhibit the development of glomerulosclerosis and also of atherosclerosis. More information also is needed also about the combination therapy with RAAS and ET receptor blockers. Studies in cellular, protein and molecular level are designed. |