RESUMEN
BACKGROUND: Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.
Asunto(s)
Arteria Braquial/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Vasodilatación/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Estudios de Casos y Controles , Adaptabilidad , Endotelio Vascular/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina , Resistencia Vascular/fisiología , VasodilatadoresRESUMEN
Angiotensin II type 1 receptor antagonist (AIIRA) has been reported to improve exercise capacity and prognosis in patients with congestive heart failure (CHF). However, the effects of AIIRA on peripheral endothelium-dependent and -independent vasodilation remain undefined in this disorder. This study examined the effects and the mechanism of chronic AIIRA therapy on peripheral vasomotion in CHF. Twenty-six patients with CHF were recruited for this study. In protocol 1, 20 patients with CHF were randomly assigned into a losartan (AIIRA) group (n = 10) and a placebo group (n = 10). Forearm blood flow (FBF; ml/min per 100 ml tissue) changes induced by intra-arterial infusion of acetylcholine, sodium nitroprusside, and synthetic angiotensin II were determined by plethysmography before and 3 months after administration of a subdepressor dose of AIIRA or placebo. The goal of protocol 2 was to determine whether the effect of AIIRA is due to a nitric oxide-dependent mechanism in the remaining subset of the CHF group (n = 6). In this group, FBF responses to acetylcholine were examined with and without coadministration of a nitric oxide synthase inhibitor (N(G)-monomethyl->L-arginine; >L-NMMA) either before and 3 months after AIIRA therapy. No significant differences were found in changes in systemic blood pressure and basal FBF among patient groups during the study period. In protocol 1, although in both groups FBF responses induced by sodium nitroprusside as well as angiotensin II remained constant throughout the study, acetylcholine-induced FBF response was significantly enhanced in the losartan group (p < 0.05) but not in the placebo group. In protocol 2, acetylcholine-induced FBF response without >L-NMMA was significantly enhanced after AIIRA administration (p < 0.05), whereas this augmentation effect was diminished under >L-NMMA coinfusion. In conclusion, selective administration of an AIIRA for 3 months improves peripheral endothelium-dependent dilation in patients with CHF. This mechanism may be independent of direct AIIRA effects and may be due, in part, to increased bioavailability of nitric oxide.