Reversal of peripheral microvascular dysfunction during long-term treatment with the angiotensin converting enzyme inhibitor fosinopril in congestive heart failure

Abstract

Background: Treatment with angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF) improves cardiac and peripheral hemodynamic function and exercise performance. However, studies on the effects of long-term treatment with an ACE inhibitor on the neurogenic and nonneurogenic regulation and structural microangiopathy of the peripheral microvasculature in CHF are lacking. Methods and Results: We investigated the effect of 12 weeks of treatment with the ACE inhibitor fosinopril on peripheral microvascular function in a double-blind, placebo-controlled study of 12 patients treated with fosinopril and 10 patients treated with placebo. All had moderate CHF. Microvascular blood flow and resistance were calculated after application of the local isotope washout method in relaxed and nonrelaxed calf vascular beds in the supine position and during head-up tilt. Skeletal muscle vascular resistance was reduced in the fosinopril group (46 ± 6 to 30 ± 1 mm Hg · mL −1 · 100 g · min ± standard error; P < .05) and differed compared with the effect of placebo ( P < .05) where no change was seen (37 ± 11 to 55 ± 13 mm Hg · mL −1 · 100 g · min; not significant [NS]). Also, skin minimal vascular resistance was reduced during fosinopril treatment (13 ± 0.6 to 11 ± 0.7 mm Hg · mL −1 · 100 g · min; ( P < .05) and differed compared with the effect of placebo ( P < .05) with absence of change (12 ± 1.6 to 14 ± 1.4 mm Hg · mL −1 · 100 g · min; NS). Conclusions: These results suggest that long-term ACE inhibitor treatment with fosinopril in patients with CHF improves hemodynamic status to as far as the peripheral microvascular level in both the relaxed and nonrelaxed microcirculation of the lower leg.