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Early-onset endothelin receptor blockade in hypertensive heterozygous Ren-2 rats.

Abstract
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.
AuthorsIvana Vanecková, Herbert J Kramer, Angela Bäcker, Stanislava Schejbalová, Zdena Vernerová, Václav Eis, Martin Opocenský, Pavel Dvorák, Ludek Cervenka
JournalVascular pharmacology (Vascul Pharmacol) Vol. 45 Issue 3 Pg. 163-70 (Sep 2006) ISSN: 1537-1891 [Print] United States
PMID16807127 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antihypertensive Agents
  • Endothelin A Receptor Antagonists
  • Endothelin B Receptor Antagonists
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Pyrrolidines
  • Receptors, Endothelin
  • Ren2 protein, mouse
  • Sodium Chloride, Dietary
  • Sulfonamides
  • Renin
  • bosentan
  • atrasentan
Topics
  • Animals
  • Animals, Genetically Modified
  • Antihypertensive Agents (pharmacology, therapeutic use)
  • Blood Pressure (drug effects)
  • Body Weight (drug effects)
  • Cardiomegaly (prevention & control)
  • Disease Models, Animal
  • Endothelin A Receptor Antagonists
  • Endothelin B Receptor Antagonists
  • Endothelin Receptor Antagonists
  • Endothelin-1 (metabolism)
  • Glomerulosclerosis, Focal Segmental (prevention & control)
  • Heterozygote
  • Hypertension (chemically induced, metabolism, physiopathology, prevention & control)
  • Male
  • Proteinuria (prevention & control)
  • Pyrrolidines (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Endothelin (metabolism)
  • Renin (genetics)
  • Sodium Chloride, Dietary
  • Sulfonamides (pharmacology, therapeutic use)
  • Time Factors

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