OXIDIZED LIPOPROTEINS INHIBIT ENDOTHELIUM-DEPENDENT VASODILATION - EFFECTS OF PRESSURE AND HIGH-DENSITY-LIPOPROTEIN

Hypertension and atherogenic low-density lipoproteins cause attenuation of endothelium-dependent dilations in vivo. We investigated a potential interference of high transmural pressure with the effects of low-density lipoproteins on endothelium-dependent dilation in vitro. Furthermore, we determined whether high-density lipoproteins preserve endothelial function. Endothelium-intact rabbit renal arteries were isolated, placed in an organ bath, perfused intraluminally with Tyrode's solution, and exposed to different degrees of transmural pressure and native or oxidized low-density lipoproteins. In preconstricted arteries perfused under low-pressure conditions (30 mm Hg), acetylcholine dose dependently elicited endothelium-dependent dilations that were not altered by increasing the perfusion pressure to 100 mm Hg for 90 minutes (high-pressure conditions). Incubation of the arteries with native or oxidized low-density lipoproteins (0.2 and 1 mg/mL for 60 minutes, respectively) under low-pressure conditions did not attenuate acetylcholine-induced dilations. However, under high-pressure conditions dilations were dose dependently attenuated by oxidized but not by native low-density lipoproteins. Endothelium-independent dilations to glyceroltrinitrate (0.001 to 3 mu mol/L) were not affected. Preincubation of the segments with high-density lipoproteins (0.5 mg/mL, 30 minutes) prevented attenuation of dilator responses. The attenuation of endothelium-dependent dilations by oxidized low-density lipoproteins under high-pressure conditions was accompanied by a transmural, dose-dependent infiltration of the vessel wall with lipoprotein, as detected by light microscopy of cryostat sections stained with Sudan III. This infiltration was prevented by high-density lipoprotein. Under low-pressure conditions no lipoprotein infiltration was visible. In segments incubated with native low-density lipoprotein, no lipoprotein infiltration was detectable. We suggest that the inhibitory effect of oxidized low-density lipoprotein on endothelium-dependent dilations is related to the arterial infiltration with lipid, which depends on the transmural pressure and is prevented by high-density lipoprotein. This mechanism may be important in patients with hypercholesterolemia and hypertension.