AT1 receptor antagonist, TCV 116, does not prevent cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats

Clin Exp Pharmacol Physiol. 1996 Apr;23(4):282-6. doi: 10.1111/j.1440-1681.1996.tb02824.x.

Abstract

1. We investigated the effects of direct blockade of angiotensin II (AngII) by a potent, non-peptide angiotensin II toff 1 (AT1) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats. 2. Six week old male Dahl salt-sensitive rats (n = 44) were fed a 4% salt diet and were simultaneously given various doses of TCV 116 orally for 7 weeks. Each control group received vehicle alone. 3. Dietary high salt intake elevated blood pressure continuously and caused left ventricular hypertrophy in rats treated with vehicle. TCV 116 had a minor effect on the rise in blood pressure. Left ventricular mass (left ventricular weight/body-weight) decreased slightly but not significantly, in rats treated with 3 mg/kg per day of TCV 116 (n = 8). Higher doses of TCV 116 (6 and 10 mg/kg per day; n = 8 each) did not show a decrease in left ventricular mass compared with the vehicle control. 4. These results suggest that AngII blockade has only minor effects on hypertension and on cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats and that the renin-angiotensin system may not contribute to the development of cardiac hypertrophy in Dahl salt-sensitive rats on a moderately high-salt diet.

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Benzimidazoles / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Blood Pressure / drug effects*
  • Body Weight
  • Dose-Response Relationship, Drug
  • Hypertension / drug therapy
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / prevention & control*
  • Male
  • Prodrugs / pharmacology*
  • Random Allocation
  • Rats
  • Sodium, Dietary / adverse effects*
  • Tetrazoles*

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Prodrugs
  • Sodium, Dietary
  • Tetrazoles
  • candesartan cilexetil