End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and late endothelin receptor blockade
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
20131938
DOI
10.33549/physiolres.931640
PII: 1640
Knihovny.cz E-zdroje
- MeSH
- antagonisté endotelinového receptoru A * MeSH
- antagonisté endotelinového receptoru B MeSH
- antihypertenziva farmakologie MeSH
- atrasentan MeSH
- bosentan MeSH
- časové faktory MeSH
- endotelin-1 metabolismus MeSH
- fokálně segmentální glomeruloskleróza genetika metabolismus patofyziologie prevence a kontrola MeSH
- heterozygot MeSH
- homozygot MeSH
- hypertenze komplikace farmakoterapie genetika metabolismus patofyziologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- kuchyňská sůl MeSH
- modely nemocí na zvířatech MeSH
- podocyty účinky léků metabolismus patologie MeSH
- potkani transgenní MeSH
- progrese nemoci MeSH
- pyrrolidiny farmakologie MeSH
- receptor endotelinu A metabolismus MeSH
- receptor endotelinu B metabolismus MeSH
- renin genetika MeSH
- sulfonamidy farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antagonisté endotelinového receptoru A * MeSH
- antagonisté endotelinového receptoru B MeSH
- antihypertenziva MeSH
- atrasentan MeSH
- bosentan MeSH
- endotelin-1 MeSH
- kuchyňská sůl MeSH
- pyrrolidiny MeSH
- receptor endotelinu A MeSH
- receptor endotelinu B MeSH
- Ren2 protein, mouse MeSH Prohlížeč
- renin MeSH
- sulfonamidy MeSH
The rat strain transgenic for the murine Ren-2 renin gene (TGR) is defined as a monogenic model of angiotensin II-dependent hypertension with endogenous activation of the renin-angiotensin system. Homozygous males TGR develop malignant hypertension with a strong salt-sensitive component. These animals show severe hypertension, proteinuria and high mortality. Morphological changes of renal parenchyma correspond to chronic ischemic glomerular changes. Heterozygous TGR develop only mild hypertension and thus provide a more suitable model of hypertension regarding to clinical studies. Within the renal parenchyma, secondary focal segmental glomerulosclerosis (FSGS) predominates. High-salt diet in heterozygous animals induces transition from benign to malignant phase of hypertension. In this case, ischemic glomerular changes are superimposed on preexisting secondary FSGS. In the regression model of hypertension (late-onset treatment) the effect of salt intake is attenuated. In homozygous TGR, early selective ET(A) receptor blockade decreased blood pressure and ameliorated end-organ damage. Late selective ET(A) receptor blockade reduced podocyte injury despite final severe hypertension. Survival rate was markedly improved in both regimens with ET(A) selective blockade, while there was only partial improvement with early non-selective blockade. Both bosentan and atrasentan decreased ET-1 levels in both regimens. In heterozygous TGR, early and late ET(A) treatment substantially while ET(A)/ET(B) treatment partially improved survival rate. Significant effect on BP was found with early and late ET(A) blockade, while ET(A)/ET(B) blockade had no effect. Bosentan and atrasentan similarly decreased ET-1 levels on both regimens. In conclusion, selective ET(A) receptor blockade is superior to nonselective ET(A)/ET(B) receptor blockade in attenuating hypertension and end-organ damage. Its effect is more pronounced when applied early in the life.
Citace poskytuje Crossref.org
Sex differences in blood pressure of aged Ren-2 transgenic rats
