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

• Published in: Arzneimittel-Forschung Vol. 47; no. 9; p. 1016
• Main Authors: Stasch, J P, Knorr, A, Hirth-Dietrich, C, Krämer, T, Hübsch, W, Dressel, J, Fey, P, Beuck, M, Sander, E, Frobel, K, Kazda, S
• Format: Journal Article
• Language: English
• Published: Germany 01.09.1997
• Subjects: 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
• ISSN: 0004-4172

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.