Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 5th communication: hemodynamic effects of valsartan in dog heart failure models.
Hemodynamic effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]meth yl¿valine, CAS 137862-53-4, CGP 48933), a non-peptide angiotensin II type 1 receptor antagonist were examined in dogs with heart failure induced acutely by coronary artery ligation and chronically by rapid-ventricular pacing. Coronary artery ligation induced decrease in cardiac output and increase in left ventricular end-diastolic pressure. Valsartan at 10 mg/kg i.v. reduced blood pressure, heart rate, left ventricular pressure, left ventricular end-diastolic pressure and total systemic resistance. Similar changes were observed with enalaprilat at 0.1 mg/kg i.v. Rapid left ventricular pacing for 2 weeks reduced cardiac contractility. Valsartan, administered at a dose of 100 mg/kg/d p.o. for 2 weeks, lowered left ventricular end-diastolic pressure. Valsartan reduced preload and afterload in these two dog heart failure models.
Yamamoto
S
S
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Hayashi
N
N
Kometani
M
M
Nakao
K
K
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013318:Stroke Volume / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000068756:Valsartan; D015773:Enalaprilat; D014633:Valine