Assessment of vascular function in systemic sclerosis: Indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production

Abstract

Objective. To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc).Methods. Endothelium-dependent (i.e., flowmediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age-and sex-matched healthy controls by highresolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt max ), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay.Results. Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt max was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules.Conclusion. The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt max . The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.

Carotid Intima Media Thickness in Systemic Sclerosis Patients: Results From a Single Centre, Cross Sectional, Case-Control Study

“…We did not find a statistically significant difference in FMD values in SSc patients as compared to controls. Other studies also support our findings [29,32]. FMD values exhibited a weak positive correlation with age (Rho=0.294; P=0.039) and an inverse correlation with serum triglycerides (Rho=-0.316; p=0.025), the same has not been reported previously [27].…”

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

“…Another study showed that flowmediated dilatation was decreased in patients with SSc compared with controls (8). Some studies found nitratemediated dilatation was reduced in SSc, suggesting coexisting functional or structural abnormalities of arterial smooth muscle, adventitia, or both (48,49). Our patient cohort had an impaired CFR with increased ADMA levels.…”

Avaliação da função endotelial em pacientes com esclerose sistêmica limitada por meio do eco Doppler da artéria braquial

“…Szucs et al 18 have found a reduction in FMD, but no change in NMD, when studying individuals with DSSc or LSSc as compared with healthy women. Andersen et al 9 have found no alterations in FMD and NMD when comparing healthy individuals with those having DSSc or LSSc. Rajagopalan et al, 21 comparing individuals with primary RP and secondary RP ANOVA for repeated measures between the two groups (effect of the interaction group*time).…”

“…They consist in thickening/proliferation/ edema of the intima layer with infi ltration of mononuclear cells, hypertrophy of the media and intima layers, rupture of the lamina elastica interna, and presence of fi brotic scars in vessel walls. 9,10 Little is known about the structural changes found in the wall of larger vessels, elastic vessels, such as the brachial, ulnar and radial arteries (conductance vessels), which can be measured by use of non-invasive techniques such as Doppler ultrasound. There is increasing evidence that the macrovasculature is also involved in the SSc disease process, which is speculated to relate to the presence of structural abnormalities, such as thickening and stiffness of the vascular wall.…”

“…However, macrovascular endothelial dysfunction in SSc has been the object of several studies, whose authors have reported a reduction in the BA fl ow-mediated dilation (FMD), [17][18][19][20] while others have not. 9,21,22 This study aimed at comparing the endothelium-dependent dilating response obtained after a fi ve-minute ischemia induced by placing a sphygmomanometer cuff in the right upper limb (FMD) and the endothelium-independent dilating response obtained after sublingual nitroglycerin administration (nitroglycerin-mediated dilation -NMD), in patients with LSSc and healthy individuals of matched gender, age and color.…”