INTRODUCTION: Endothelial dysfunction is an early event in the development of atherosclerotic disease. We investigated endothelial function in the peripheral circulation of patients with undifferentiated connective tissue diseases (UCTDs), in comparison to healthy controls. METHODS: In 15 young UCTD patients (mean age 39 years) with inactive disease and without cardiovascular risk factors and in 15 age-matched controls we evaluated endothelial function in the brachial conduit artery and in the forearm microcirculation. The first district was assessed by flow mediated dilation (FMD) and response to glyceryl trinitrate, and forearm microcirculation by blood flow changes (strain-gauge venous plethysmography) in response to intra-arterial acetylcholine (Ach) and sodium nitroprusside (SNP). Nitric oxide (NO) availability was evaluated by repeating Ach in the presence of intraarterial N(G)-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor. RESULTS: FMD and response to GTN were similar in UCTD patients and controls. UCTD patients showed a reduced response to Ach (P<0.001) and SNP (P<0.01) as compared to controls. In healthy controls l-NMMA infusion significantly (P<0.001) reduced the vascular response to Ach, while in UCTD patients l-NMMA failed to affect vasodilation to Ach. In UCTD patients, vascular responses were unrelated to clinical manifestations or autoantibody profile. CONCLUSIONS: Young UCTD patients are characterized by reduced endothelium-dependent and -independent vasodilation in the forearm microcirculation, but not in peripheral conduit arteries. Reduced NO availability was indirectly observed. These results suggest that in the absence of traditional risk factors, inactive systemic autoimmune diseases impair NO-dependent but also endothelium-independent vasodilation selectively in the microcirculation.
INTRODUCTION: Endothelial dysfunction is an early event in the development of atherosclerotic disease. We investigated endothelial function in the peripheral circulation of patients with undifferentiated connective tissue diseases (UCTDs), in comparison to healthy controls. METHODS: In 15 young UCTD patients (mean age 39 years) with inactive disease and without cardiovascular risk factors and in 15 age-matched controls we evaluated endothelial function in the brachial conduit artery and in the forearm microcirculation. The first district was assessed by flow mediated dilation (FMD) and response to glyceryl trinitrate, and forearm microcirculation by blood flow changes (strain-gauge venous plethysmography) in response to intra-arterial acetylcholine (Ach) and sodium nitroprusside (SNP). Nitric oxide (NO) availability was evaluated by repeating Ach in the presence of intraarterial N(G)-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor. RESULTS:FMD and response to GTN were similar in UCTD patients and controls. UCTD patients showed a reduced response to Ach (P<0.001) and SNP (P<0.01) as compared to controls. In healthy controls l-NMMA infusion significantly (P<0.001) reduced the vascular response to Ach, while in UCTD patientsl-NMMA failed to affect vasodilation to Ach. In UCTD patients, vascular responses were unrelated to clinical manifestations or autoantibody profile. CONCLUSIONS: Young UCTD patients are characterized by reduced endothelium-dependent and -independent vasodilation in the forearm microcirculation, but not in peripheral conduit arteries. Reduced NO availability was indirectly observed. These results suggest that in the absence of traditional risk factors, inactive systemic autoimmune diseases impair NO-dependent but also endothelium-independent vasodilation selectively in the microcirculation.
Authors: Pal Soltesz; Daniel Bereczki; Peter Szodoray; Maria T Magyar; Henrietta Der; Istvan Csipo; Agota Hajas; Gyorgy Paragh; Gyula Szegedi; Edit Bodolay Journal: Arthritis Res Ther Date: 2010-05-06 Impact factor: 5.156