Effect of repeated administration of KT3-671, a nonpeptide AT1 receptor antagonist, on diurnal variation in blood pressure, heart rate, and locomotor activity in stroke-prone spontaneously hypertensive rats as determined by radiotelemetry.
KT3-671, a nonpeptide AT1 receptor antagonist, was administered to 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) daily for 3 weeks. Its effects on systolic, mean, and diastolic arterial blood pressure (SAP, MAP, DAP), heart rate and locomotor activity were investigated with radiotelemetry. A clear diurnal variation in blood pressure, heart rate, and locomotor activity was observed in synchrony with the light cycle. KT3-671 at a daily dose of 10 mg/kg orally (p.o), produced a significant and consistent reduction in blood pressure, preventing the development of hypertension. KT3-671 reduced SAP more than DAP, suggesting that it may affect both vascular tone and cardiac output. Although KT3-671 did not affect diurnal rhythms in heart rate and locomotor activity, it did cause a slight but significant reduction in heart rate. The MAP determined 23 h after the administration of KT3-671 showed a significant reduction from the day 2 of therapy to the day 3 after discontinuation of therapy, suggesting a long duration of antihypertensive action. There was no rebound increase in blood pressure after discontinuation of KT3-671 therapy. These results suggest that KT3-671 may be potentially useful in the therapy of hypertension.
Kawashima
K
K
Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku, Tokyo, Japan.
Amano
H
H
Fujimoto
K
K
Suzuki
T
T
Fujii
T
T
Mochizuki
S
S
Tomiyama
A
A
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; C093160:KT3 671; D013777:Tetrazoles