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Antihypertensive activity of a nonpeptide angiotensin II receptor antagonist, YM358, in rats and dogs

, : Antihypertensive activity of a nonpeptide angiotensin II receptor antagonist, YM358, in rats and dogs. European Journal Of Pharmacology. 335(2-3): 175-184

The antihypertensive activity of YM358, 2,7-diethyl-5-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-5H-pyrazolo(1,5-b)(1,2,4)triazole potassium salt monohydrate, a new nonpeptide angiotensin II receptor antagonist, was characterized in rats and dogs. In conscious rats, YM358 after a single oral administration (1-30 mg/kg) lowered blood pressure. The rank order of hypotensive potency of YM358 in conscious rats was 2-kidney, 1-clip renal hypertensive rats gt spontaneously hypertensive rats gt normotensive rats on the basis of maximum hypotension. YM358 also caused decreases in blood pressure in 2-kidney, 1-clip renal hypertensive dogs and furosemide-treated dogs. Repeated administration of YM358 to 2-kidney, 1-clip renal hypertensive rats for 28 days produced a stable and long-lasting antihypertensive effect without influencing circadian blood pressure and heart rate rhythms. No reflex tachycardia was observed in any animals of either species treated with YM358. Therefore, the pharmacological profile of this compound indicates that YM358 has potential as a useful antihypertensive agent.

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Accession: 008173051

DOI: 10.1016/s0014-2999(97)01190-4

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