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 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Galle
J
J
Department of Medicine, University Hospital of Freiburg, Germany.
Ochslen
M
M
Schollmeyer
P
P
Wanner
C
C
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010084:Oxidation-Reduction; D011312:Pressure; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D009569:Nitric Oxide