Long-term blockade of the angiotensin II receptor in renin transgenic rats, salt-loaded Dahl rats, and stroke-prone spontaneously hypertensive rats.
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.
Stasch
J P
JP
Bayer AG, Institute of Cardiovascular Research, Wuppertal, Germany.
Knorr
A
A
Hirth-Dietrich
C
C
Krämer
T
T
Hübsch
W
W
Dressel
J
J
Fey
P
P
Beuck
M
M
Sander
E
E
Frobel
K
K
Kazda
S
S
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology*; D006152:Cyclic GMP / Q000097:blood; D004095:Dihydropyridines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004095:Dihydropyridines; D006728:Hormones; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; C109119:embusartan; D009320:Atrial Natriuretic Factor; D012083:Renin; D006152:Cyclic GMP