Effects of high-density lipoprotein on endothelium-dependent vasorelaxation

Studies using cultured endothelial cells have shown that high-density lipoprotein (HDL) positively modulates endothelial nitric oxide synthase (eNOS). The purpose of this study was to test the hypotheses that positive modulation of eNOS by HDL occurs in whole vessels and that it augments endothelium-dependent vasorelaxation. To test these hypotheses, brachial arteries were obtained from swine. Endothelium-dependent and endothelium-independent vasorelaxation were determined in vitro to assess the effects of acute administration of HDL (50 μg·mL–1; n = 8) and chronic exposure to relatively high HDL concentration on vascular function (low HDL, 0.89 ± 0.02 mmol·L–1, n = 4; high HDL, 1.16 ± 0.05 mmol·L–1, n = 4; p < 0.005). Acute administration of HDL did not augment maximal endothelium-dependent vasorelaxation to bradykinin (BK) (no HDL, 82.6% ± 2.2%; HDL, 76.7% ± 3.5%; not significant (ns)). Similarly, maximal relaxation to BK was not enhanced by chronic exposure to high HDL concentrations. NO synthase (NOS) activity was also similar between groups (low HDL, 129.0 ± 19.2 counts·h–1·μg–1 protein; high HDL, 113.9 ± 47.1 counts·h–1·μg–1; ns). Consistent with NOS activity, the extent of eNOS phosphorylation at several sites was similar between low HDL and high HDL. Both apolipoprotein A-I (ApoA-I) and scavenger receptor class B type I (SR-BI) were associated with eNOS. Similar to cultured cell studies, this study demonstrates that both ApoA-I and SR-BI associate with eNOS in the vascular wall. Binding of ApoA-I and SR-BI to eNOS does not, however, result in modulation of either NO formation or endothelial function.