title: Antihypertensive effect of chronic KT3-671, a structurally new nonpeptide angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.
abstract: KT3-671 (2-propyl-8-oxo-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)methyl]-4,5,6, 7-tetrahydrocycloheptimidazole), a structurally new nonpeptide angiotensin AT1-receptor antagonist, was administered orally and repeatedly to 15-week-old stroke-prone spontaneously hypertensive rats for 7 weeks; and its effects on blood pressure, heart rate, renal function, plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and hypertension-related tissue damage in the brain, heart, kidney and mesenteric artery were investigated. KT3-671 at a dose of 3 or 10 mg/kg, p.o. per day prevented development of hypertension and produced a significant and consistent reduction of blood pressure in a dose-dependent manner. Enalapril at a dose of 10 mg/kg per day produced cardiovascular effects similar to those of KT3-671 at 10 mg/kg. Despite marked reduction in blood pressure, neither KT3-671 nor enalapril affected the heart rate. KT3-671 at 10 mg/kg produced a transient and significant reduction of urinary sodium excretion in the second week, but did not affect renal function at any other time during the experimental period. Both KT3-671 at 10 mg/kg and enalapril at 10 mg/kg produced a significant increase in PRC and showed a tendency to decrease PAC. Repeated administration of KT3-671 reduced the severity of the pathological changes in the kidney. These results suggest that KT3-671 is a potentially useful antihypertensive drug.
authors.affiliation: Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Amano
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Mochizuki
authors.forename: A
authors.initials: A
authors.lastname: Tomiyama
authors.forename: K
authors.initials: K
authors.lastname: Kawashima
mesh_terms: D000450:Aldosterone / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014554:Urination / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; C093160:KT3 671; D013777:Tetrazoles; D000450:Aldosterone; D012083:Renin