Effects of orthostatic stress on forearm endothelial function in normal subjects and in patients with hypertension, diabetes, or both diseases

Background: Sympathetically mediated vasoconstriction, to compensate for reduced venous return and cardiac output, characterizes the circulatory adaptation to head-up tilting (HUT). It has not been clarified whether this is coupled with a modulating endothelial vasorelaxation and whether diseases causing endothelial dysfunction, such as diabetes and hypertension, may impair this counterregulatory mechanism. Methods: In patients with hypertension (group 1), diabetes (group 2), or both diseases (group 3) and in healthy control subjects (12 subjects per group) we investigated the brachial artery vasodilating response to the release of distal circulatory arrest (DCA) while they were supine and during 60 degrees HUT. Results: The supine increase in lumen was smaller (P <.01) in groups 1 (+4.5% +/- 1.5%), 2 (+4.8% +/- 1.4%), and 3 (+3.9% +/- 1.3%) than in the control group (+8.6% +/- 1.6%). Vasorelaxation by nitroglycerin was similar in each population. During HUT, the lumen response to DCA was enhanced (P <.01 v supine) in control subjects (+15.4% +/- 2.5%) and group 1 (+ 10.0 +/- 2.4%) and was reduced (P <.01 v supine) in groups 2 (+2.9% +/- 0.5%) and 3 (+2.1% +/- 0.4%), even though the hyperemic reaction to DCA was similar. The ratio of lumen changes to changes in flow (mm/mL/min X 1000) during reactive hyperemia to DCA increased (P <.01) with HUT, compared with that in the supine position, in control subjects (1.75 v 1.19) and group 1 (1.61 v 0.95), and decreased (P <.01) in groups 2 (0.62 v 0.87) and 3 (0.48 v 0.77). Conclusions: The HUT posture is characterized by an increased endothelium-dependent, flow-mediated vasodilation as a possible modulator of the neural vasoconstriction. This effect is persistent but blunted in hypertension and is abolished in diabetes, either alone or in association with high BP. Thus, vasoconstrictor factors could remain unmodulated during an event such as orthostasis, making the risk posed by these disorders more critical.