Assessment of microvascular reactivity and oxidative stress in hypertensive adolescents and hemodialysis patients

Abstract

The microvascular responses to endothelium-dependent and -independent vasodilators (ACH and SNP, respectively) and to local heating were studied in adolescents with primary hypertension grouped according to their BMI (LH, OWH and OBH). It emerged that the endothelium dependent vasorelaxation was not significantly attenuated in any of the hypertensive groups. This finding does not support the (otherwise clinically attractive) hypothesis of predicting the development of juvenile hypertension via noninvasive assessment of the endothelial function with LDF. In contrast, the endothelium-independent vasodilation was significantly impaired in the LH and OBH patients as compared with the controls. The microvascular reactivities were not related to differences in the levels of oxidative markers, even if the presence of an increased oxidative stress was confirmed in all the hypertensive groups. Prospective studies on larger populations of adolescents, which also assess the mechanisms of the microvascular responses to different stimuli, could clarify these issues. An impairment of the endothelium-dependent and -independent vasodilations and the presence of a markedly increased oxidative stress were confirmed in HD patients. Among possible factors influencing the oxidative stress, substantial characteristics of ESA treatment (type and withdrawal of ESA) were studied. A significant elevation of the ratio GSSG/GSH was revealed directly after the interruption of epoetin beta treatment. Four weeks after darbepoetin alfa or epoetin beta therapy resumption, the levels of GSSG/GSH, GSSG and E-MDA were significantly increased in both groups as compared with the baseline. In line with the reported antioxidant effect of the sustained ESA administration, these parameters had returned to the baseline values by the end of the 12-week follow-up, parallelled with increased GSH and E-CAT activity levels. The findings of an opposite trend in the levels of Hb and oxidative markers, and similarities in the time courses and magnitudes of the oxidative alterations during the treatment with different ESAs suggest that the observed changes may primarily be caused byfactors associated with the correction of anemia, rather than the direct effect of ESA. This emerging hypothesis is yet to be confirmed.