Early-onset endothelin receptor blockade in hypertensive heterozygous Ren-2 rats.
Male heterozygous Ren-2 transgenic rats and Hannover Sprague-Dawley rats fed a normal or high-salt diet were either untreated or treated with the nonselective receptor ET(A)/ET(B) receptor blocker bosentan or the selective ET(A) receptor blocker, ABT-627, known as atrasentan. Survival rate was partly increased by bosentan and fully normalized by atrasentan. Bosentan did not significantly influence the course of hypertension in TGR, whereas atrasentan significantly decreased BP on both diets. Atrasentan substantially reduced proteinuria, cardiac hypertrophy, glomerulosclerosis and left ventricular ET-1 tissue concentration on both diets. Our data indicate that ET(A) receptor blockade is superior to nonselective blockade in attenuating hypertension, end-organ damage and improving survival rate.
Vanecková
Ivana
I
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. ivvn@medicon.cz
Kramer
Herbert J
HJ
Bäcker
Angela
A
Schejbalová
Stanislava
S
Vernerová
Zdena
Z
Eis
Václav
V
Opocenský
Martin
M
Dvorák
Pavel
P
Cervenka
Ludek
L
D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D006332:Cardiomegaly / Q000517:prevention & control; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D006579:Heterozygote; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D011507:Proteinuria / Q000517:prevention & control; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D012083:Renin / Q000235:genetics*; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D017466:Receptors, Endothelin; C473112:Ren2 protein, mouse; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; D012083:Renin; D000077300:Bosentan; D000077868:Atrasentan