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 loco-motor 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. Al-though 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.