Long-term blockade of the angiotensin II receptor in renin transgenic rats, salt-loaded Dahl rats, and stroke-prone spontaneously hypertensive rats

Arzneimittelforschung. 1997 Sep;47(9):1016-23.

Abstract

These studies were designed to investigate the protective effects of the new angiotensin II receptors antagonist BAY 10-6734 (6-n-butyl-4-methoxycarbonyl-2-oxo-1[(2'-(1H-tetrazol-5-yl) -3-fluorobiphenyl-4-yl)methyl] 1,2-dihydropyridine, CAS 156001-18-2) on haemodynamic, hormonal, renal, and structural parameters in renin transgenic rats (TGR(mRen2)27), salt-loaded Dahl S and R rats, and salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SP) in long-term trials. Study 1: In SHR-SP the development of blood pressure, cardiac hypertrophy, and the deleterious effects of salt loading on kidney structure and kidney function was prevented by BAY 10-6734. Study 2: In salt-loaded Dahl S rats with a suppressed plasma renin activity treatment with BAY 10-6734 did not delay the increase in blood pressure but prevented cardiac hypertrophy and the increase in plasma ANP (Atrial natriuretic peptide). Study 3: TGR develop malignant hypertension associated with cardiac hypertrophy, elevated left-ventricular end-diastolic pressure and increased plasma ANP. After 6 weeks of treatment with BAY 10-6734 (30 mg/kg p.o. bid) cardiac pump function was improved and cardiac hypertrophy was reversed in this angiotension dependent form of hypertension. The beneficial effects of BAY 10-6734 in these different animal hypertension models are also emphasized by a reduction in mortality.

MeSH terms

  • Aldosterone / blood
  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists*
  • Animals
  • Animals, Genetically Modified
  • Antihypertensive Agents / pharmacology*
  • Atrial Natriuretic Factor / blood
  • Body Weight / drug effects
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / physiopathology*
  • Cyclic GMP / blood
  • Dihydropyridines / pharmacology*
  • Hemodynamics / drug effects
  • Hormones / blood
  • Hypertension / chemically induced
  • Hypertension / genetics
  • Hypertension / prevention & control*
  • Kidney / pathology
  • Kidney / physiopathology
  • Rats
  • Rats, Inbred SHR
  • Renin / genetics*
  • Tetrazoles / pharmacology*

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Dihydropyridines
  • Hormones
  • Tetrazoles
  • Angiotensin II
  • Aldosterone
  • embusartan
  • Atrial Natriuretic Factor
  • Renin
  • Cyclic GMP