Low-dose combination of at II receptor blockade and ACE-inhibition in mild hypertension

Abstract

Cclinical studies on the effects of angiotensin-converting enzyme inhibitors support the central role of Angiotensin II, able to cause cardiovascular and renal diseases independently of its blood pressure elevating effects. The evaluation of cardiovascular adjustments to head-up tilt represents an easy method to test the ability of the reflex mechanisms to maintain blood pressure homeostasis and to assess the baroreflex by means of a natural stimulation. The present study was aimed at evaluating the effect(s) of three different pharmacological regimens on baroreflex sensitivity in uncomplicated essential hypertension, by means of continuos and non-invasive beat to beat heart rate and blood pressure measurements during head-up tilt. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an angiotensin AT1-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomized, single-blind, crossover fashion for a period of three weeks each to twelve mild essential hypertensives (6 females, mean age 42 ± 1 years). A 60° head-up tilt test was performed at the end of each drug period and norepinephrine plasma levels were measured. Baroreflex function measured with the “tilting method” was calculated as the slope of the linear regression line relating systolic blood pressure changes to RR changes during upward and downward phases of tilting, respectively. The low-dose combination therapy induced the greatest reduction in blood pressure, in the resting as well as in the tilted position, associated with an increased slope in the baroreflex sensitivity. Norepinephrine plasma levels were lower after combined therapy (Table). Our results suggest that in mild essential hypertension, the low dose combination is associated with an improved baroreflex sensitivity as well as a reduction in both blood pressure and sympathetic drive (as inferred by the reduced values of norepinephrine). Thus, the combined interruption of the RAS system may be a more effective strategy to reduce cardiovascular risk.