Effect of losartan on heart rate and blood pressure variability during tilt test and trinitroglycerine vasodilation

Objective To define the changes in variability of heart rate and of blood pressure during vasodilation in a group of hypertensive patients treated with an angiotensin II type I (AT1) receptor inhibitor. Design Losartan (50 mg/day at 0800 h) or placebo were administered for 3 weeks according to a single blind, crossover, randomized protocol, to 18 hypertensive patients (16 men and two women, mean age 42 +/- 3.6 years). Continuous ECG recording and beat-to-beat blood pressure monitoring were carried out with subjects in the supine position and during a head-up tilt test, as well as after sublingual administration of trinitroglycerine. The elaboration of ECG traces in the frequency domain, was carried out using an autoregressive method and measured using the autoregressive moving average technique. Results Orthostatic stimulus, both during treatment with losartan and with placebo, caused a significant decrease in the heart rate high frequency power; on the other hand, the low frequency power appeared unchanged after placebo and was significantly reduced with losartan. Five minutes after the administration of trinitroglycerine, the low frequency power with placebo showed a significant increase (817 +/- 221 versus 465 +/- 101 ms(2), P < 0.03). No change was recorded in total power nor in low frequency or high frequency power during losartan therapy. The ratio of low frequency to high frequency powers showed a sympathetic prevalence during vasodilation only during placebo treatment, whereas a mainly unchanged balance was maintained during losartan treatment Blood pressure variability showed a sympathetic prevalence after upright and trinitroglycerine stimulation only in placebo-treated subjects. Conclusions Our study demonstrated that vasodilation is not able to evoke an unbalancing of the autonomic modulation in hypertensive patients treated with an AT1 receptor inhibitor, but permits the maintenance of a significant vagal component, thus highlighting the favorable profile of this drug in the autonomic control of circulation. J Hypertens 1999, 17:513-521 (C) Lippincott Williams & Wilkins.