Early endothelin-A receptor blockade decreases blood pressure and ameliorates end-organ damage in homozygous Ren-2 rats
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16157796
DOI
10.1161/01.hyp.0000173426.06832.b5
PII: 01.HYP.0000173426.06832.b5
Knihovny.cz E-resources
- MeSH
- Survival Analysis MeSH
- Endothelin A Receptor Antagonists * MeSH
- Atrasentan MeSH
- Bosentan MeSH
- Endothelin-1 antagonists & inhibitors MeSH
- Glomerulosclerosis, Focal Segmental pathology MeSH
- Animals, Genetically Modified MeSH
- Hypertension etiology metabolism physiopathology MeSH
- Cardiomegaly pathology MeSH
- Blood Pressure * MeSH
- Rats MeSH
- Sodium Chloride, Dietary MeSH
- Kidney pathology MeSH
- Myocardium metabolism MeSH
- Osmolar Concentration MeSH
- Rats, Sprague-Dawley MeSH
- Proteinuria physiopathology MeSH
- Pyrrolidines pharmacology MeSH
- Renin metabolism MeSH
- Heart Ventricles MeSH
- Sulfonamides pharmacology MeSH
- Body Weight MeSH
- Organ Size MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endothelin A Receptor Antagonists * MeSH
- Atrasentan MeSH
- Bosentan MeSH
- Endothelin-1 MeSH
- Sodium Chloride, Dietary MeSH
- Pyrrolidines MeSH
- Ren2 protein, mouse MeSH Browser
- Renin MeSH
- Sulfonamides 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.
References provided by Crossref.org
Research on Experimental Hypertension in Prague (1966-2009)
