• MeSH
• angiotensin II sekrece   MeSH
• elektronová mikroskopie MeSH
• epitelové buňky MeSH
• juxtaglomerulární aparát cytologie   sekrece   MeSH
• ledviny fyziologie   MeSH
• lidé MeSH
• osmolární koncentrace MeSH
• renin sekrece   MeSH
• zpětná vazba MeSH
• Check Tag
• lidé MeSH

We have recently found that nonselective endothelin ETA/ETB receptor blockade markedly improves survival rate and ameliorates end-organ damage in male homozygous rats transgenic (TGR) for the mouse Ren-2 renin gene without lowering blood pressure. Because activation of the ETA receptor may be responsible for the detrimental effects of ET in the development of hypertension, this study was performed to determine whether ETA or ETA/ETB receptor blockade exerts these beneficial effects. TGR and age-matched normotensive Hannover Sprague-Dawley rats fed a high-salt diet received either vehicle or bosentan and atrasentan (ABT-627) as nonselective ETA/ETB and selective ETA receptor blockers, respectively, from 29 until 90 days of age. The survival rate of 48% in untreated TGR was significantly (P<0.01) improved to 79% by bosentan and to 92% by ABT-627 (ABT-627 versus bosentan P<0.05). Proteinuria, glomerulosclerosis, and cardiac hypertrophy, as well as ET-1 content in left ventricular tissue, were significantly reduced by bosentan and to a greater degree by ABT-627, which also significantly attenuated the rise in blood pressure (P<0.05). Our data indicate that the ET system, especially via ETA receptors, plays an important role in the development of hypertensive end-organ damage and confirm the concept that the predominant role of ETB receptors within the peripheral vasculature is to mediate the vasorelaxant actions of ET-1. They also demonstrate that selective blockade of ETA receptors is superior to nonselective ETA/ETB in attenuating hypertension, hypertensive organ damage, and survival rate.

• MeSH
• analýza přežití MeSH
• antagonisté endotelinového receptoru A MeSH
• endotelin-1 antagonisté a inhibitory   MeSH
• fokálně segmentální glomeruloskleróza patologie   MeSH
• geneticky modifikovaná zvířata MeSH
• hypertenze etiologie   metabolismus   patofyziologie   MeSH
• kardiomegalie patologie   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl MeSH
• ledviny patologie   MeSH
• myokard metabolismus   MeSH
• osmolární koncentrace MeSH
• potkani Sprague-Dawley MeSH
• proteinurie patofyziologie   MeSH
• pyrrolidiny farmakologie   MeSH
• receptor endotelinu A MeSH
• renin metabolismus   MeSH
• sulfonamidy farmakologie   MeSH
• tělesná hmotnost MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH