Hemodynamic and autonomic evaluations were carried out after 2-3 weeks of treatment with placebo and at the end of 4 weeks of treatment with an angiotensin converting enzyme (ACE) inhibitor, trandolapril, 2 mg/day in 18 hypertensive patients (average age, 48 +/- 2 years) of either sex. This treatment lowered the mean arterial pressure in the whole group from 112 to 105 mm Hg (p < 0.05) without significant changes in basal heart rate or norepinephrine (NE) and epinephrine plasma levels. Based on daytime ambulatory blood pressure monitoring, the patients were separated into 2 equal groups of 9 patients: the better responders (R), with an average decrease in mean arterial pressure of 12 mm Hg, and the lesser responders (NR), with an average fall of mean arterial pressure of 2 mm Hg. Before treatment, the R group had a higher resting heart rate, a lower cardiac output (-16%), and a higher peripheral resistance (+22%) than the NR group (difference not significant). Moreover, the R group was also observed to have a 33% higher plasma NE level (p < 0.05) in the supine position, associated with a 52% higher NE response to standing (p < 0.05), and a 40% lower number of beta-adrenergic receptors on lymphocytes, suggesting a higher sympathetic tone and reactivity in that group. Following treatment with the ACE inhibitor, heart rate and plasma NE levels were not altered significantly in either group, suggesting a blunting of the baroreflex response concomitant with the lowered blood pressure, especially in the R group. The cardiac output was unchanged in both groups, but the peripheral resistance decreased by 10% only in the R group (difference not significant). The NE responses to standing and to Isometric exercise were attenuated to a greater extent in the R group than in the NR group: -21% versus -14% and -43% versus -7%, respectively. The numbers of beta adrenoceptors on lymphocytes were similarly increased by 100% In both groups following this therapy. It is concluded from these studies that patients presenting evidence of increased sympathetic tone and reactivity may be better responders to ACE inhibitor therapy. In fact, treatment with trandolapril was shown to reduce blood pressure and peripheral resistance, in part by attenuating the sympathetic reactivity to a greater extent in the subset of ''responders,'' presumably by interfering with the angiotensin II-mediated facilitatory presynaptic mechanisms located on peripheral sympathetic fibers.
