Chronic ACE Inhibition Enhances the Endothelial Control of Arterial Mechanics and Flow-Dependent Vasodilatation in Heart Failure

Abstract

Abstract-Reduced conduit arteries flow-dependent dilatation and altered compliance have been described during heart failure. However, the role of shear stress, the relation between endothelial dysfunction and mechanics, and the effect of chronic ACE inhibition on this relationship have not been investigated. The present study was designed to evaluate in heart failure patients the relationship between flow-dependent dilatation and radial artery mechanics at known shear stress levels and to assess the effect of chronic ACE inhibition. Sixteen stable congestive heart failure patients, who had never been treated with ACE inhibitors, participated in the study. Arterial pressure, cardiac output (bioimpedance), radial artery diameter (echo tracking) and flow (Doppler), total blood viscosity, and mean artery wall shear stress were assessed before and during a gradual increase in the forearm blood flow in response to gradual distal hand skin heating. Cross-sectional radial artery compliance and distensibility indexes were calculated at 34°C, 40°C, and 44°C. The endothelium-independent vasodilatation was evaluated by use of glyceryl trinitrate. All parameters were assessed before and 24 hours after the last administration of perindopril (4 mg once daily) or placebo in a 2-month double-blind randomized study. Before treatment, there was no difference between the 2 groups for all parameters. After chronic ACE inhibition, systolic arterial pressure decreased at baseline from 126Ϯ11 to 118Ϯ10 mm Hg (PϽ0.05). During heating, the increase in diameter in response to shear stress was higher after ACE inhibition than after placebo (time/treatment interaction, PϽ0.05). Moreover, in contrast to placebo, at the same shear stress, there was a significant increase in compliance (3.23Ϯ0.79ϫ10 Ϫ7 to 6.82Ϯ2.47ϫ10 Ϫ7 m 2 /kPa, PϽ0.05) and distensibility (5.71Ϯ1.35ϫ10 Ϫ3 to 8.87Ϯ1.88ϫ10 Ϫ3 /kPa, PϽ0.05) during heating after ACE inhibition. The effect of glyceryl trinitrate did not change. The present study demonstrates that chronic administration of the ACE inhibitor perindopril increases the magnitude of the flow-dependent dilatation and restores the flow-dependent increase in compliance and distensibility of the radial artery evaluated at stable shear stress. In addition, the decrease in baseline systolic arterial pressure after ACE inhibitor suggests an associated increase in the distensibility of the proximal elastic conduit arteries. (Hypertension. 2001;38: 1446-1450.) Key Words: arteries Ⅲ endothelium Ⅲ flow-mediated Ⅲ elasticity Ⅲ angiotensin-converting enzyme inhibitors E ndothelium mediates flow-dependent vasodilatation and contributes to the regulation of arterial mechanics by releasing vasoactive factors that modify arterial tone and trophicity. [1][2][3][4][5] In heart failure, reduced conduit artery flowdependent dilatation and altered arterial compliance have been described. 4,6 -11 Moreover, reduced increase in distensibility during exercise also contributes to an increase in left ventricular afterload and an inadequate card...

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