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

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.

• Authors: J P Stasch, A Knorr, C Hirth-Dietrich, T Krämer, W Hübsch, J Dressel, P Fey, M Beuck, E Sander, K Frobel, S Kazda
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 47 Issue 9 Pg. 1016-23 (Sep 1997) ISSN: 0004-4172 [Print] Germany
• PMID: 9342414 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, physiopathology)
• Cyclic GMP (blood)
• Dihydropyridines (pharmacology)
• Hemodynamics (drug effects)
• Hormones (blood)
• Hypertension (chemically induced, genetics, prevention & control)
• Kidney (pathology, physiopathology)
• Rats
• Rats, Inbred SHR
• Renin (genetics)
• Tetrazoles (pharmacology)