Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II

Abstract

Objective: To determine directly the contribution of angiotensin II to basal and sympathetically stimulated peripheral arteriolar tone in patients with heart failure.

Design: Parallel group comparison.

Subjects: Nine patients with New York Heart Association grade II-IV chronic heart failure, and age and sex matched controls.

Interventions: Forearm plethysmography, lower body negative pressure, local intra-arterial administration of losartan, angiotensin II, and noradrenaline, and estimation of plasma hormone concentrations.

Main outcome measures: Forearm blood flow responses, plasma hormone concentrations.

Results: Baseline blood pressure, heart rate, and forearm blood flow did not differ between patients and controls. In comparison with the non-infused forearm, losartan did not affect basal forearm blood flow (95% confidence interval -5.5% to +7.3%) or sympathetically stimulated vasoconstriction in controls. However, the mean (SEM) blood flow in patients increased by 13(5)% and 26(7)% in response to 30 and 90 micrograms/min of losartan respectively (p < 0.001). Lower body negative pressure caused a reduction in forearm blood flow of 20(5)% in controls (p = 0.008) and 13(5)% (p = 0.08) in patients (p = 0.007, controls v patients). Blood flow at 90 micrograms/min of losartan correlated with plasma angiotensin II concentration (r = 0.77; p = 0.03). Responses to angiotensin II and noradrenaline did not differ between patients and controls.

Conclusions: Losartan causes acute local peripheral arteriolar vasodilation in patients with heart failure but not in healthy control subjects. Endogenous angiotensin II directly contributes to basal peripheral arteriolar tone in patients with heart failure but does not augment sympathetically stimulated peripheral vascular tone.

Figure 1

Absolute (non-infused arm, squares; infused arm, triangles) and percentage change in forearm blood flow responses (circles), with intermittent application (arrows) of lower body negative pressure (LBNP), to saline and losartan (30 and 90 µg/min) infusion in healthy control subjects (empty symbols) and patients with heart failure (filled symbols). *p < 0.001 (one way ANOVA, v baseline saline infusion); †p = 0.008 (two way ANOVA, basal v LBNP).

Figure 2

Forearm blood flow responses to infusion of angiotensin II (squares) and noradrenaline (circles) in healthy control subjects (empty symbols) and patients with heart failure (filled symbols); p < 0.001 (one way ANOVA for each response).