Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 2nd communication: valsartan prevents end-organ damage in spontaneously hypertensive stroke-prone rats during 1-year treatment.
Valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl¿ valine, CAS 137862-53-4, CGP 48933), a non-peptide angiotensin II type 1 receptor antagonist, or enalapril was administered to spontaneously hypertensive rats stroke-prone (SHR-SP) for 1 year from 8 weeks to 56 weeks of age under a normal diet without saline load. During 48 weeks, control rats showed increase in systolic blood pressure from 180 to 250 mmHg accompanying stroke-related behaviour, cardiac and aortic hypertrophy, hyperreactive contractility of mesenteric vascular beds, proteinuria, high water turnover and death. Valsartan at 3, 10 and 30 mg/kg/d p.o. and enalapril at 1 and 10 mg/kg/d p.o suppressed the increase in blood pressure dose-dependently. Systolic blood pressure was steadily controlled to around 180 mmHg at the highest dose of either drug throughout the study. In proportion to the antihypertensive action of the drugs, end-organ damage was prevented. During 1-year administration, effects of enalapril and valsartan were much the same, indicating the clinical usefulness of valsartan being comparable to enalapril.
Kometani
M
M
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Hayashi
N
N
Yamamoto
S
S
Nakao
K
K
Inukai
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D002561:Cerebrovascular Disorders / Q000517:prevention & control / Q000652:urine; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology / Q000652:urine; D008297:Male; D008643:Mesentery / Q000098:blood supply; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D014633:Valine