Albumin restores lysophosphatidylcholine-induced inhibition of vasodilation in rat aorta

Background. Impairment of vasodilation by oxidized low-density lipoprotein has been attributed to lysophosphatidylcholine (LPC). Albumin avidly binds LPC. Therefore, hypoalbuminemia may directly impair vasodilation and thus c ontribute to increased risk of atherosclerosis in nephrotic syndrome. The a ddition of albumin reduces LPC in erythrocytes and endothelial cells. We hy pothesized that the addition of albumin will salvage vasodilation in aortic rings previously exposed to LPC. LPC increases superoxide production and d isturbs L-arginine availability. Therefore, we also decreased superoxide wi th a superoxide dismutase mimic, MnCl2, and supplemented L-arginine in an a ttempt to restore vasodilation. Methods. Rat aorta rings, which had been incubated with various concentrati ons of LPC and human serum albumin (HSA), were mounted in organ chambers. R elaxation was studied with acetylcholine (0.01 to 100 mu mol/L) after preco ntraction with phenylephrine (CON, 0.3 mu mol/L; LPC, 0.03 mu mol/L). In so me studies MnCl2 or L-arginine was added to the organ chamber. Results. LPC had time- and dose-dependent inhibitory effects on acetylcholi ne-mediated vasodilation, but no effect on nitroprusside-mediated vasodilat ion. Preincubation with albumin (50 or 6 g/L) could protect vasodilation ag ainst very high levels of LPC. After preincubation with LPC, the addition o f albumin to the incubation salvaged vasodilation. Albumin was more effecti ve after short LPC incubation. MnCl2 had no specific effect on the LPC-medi ated disturbance in vasodilation. L-arginine completely salvaged vasodilati on at low concentrations of LPC. However, even high concentrations Of L-arg inine (I mmol/L) could not improve vasodilation at LPC levels at which vaso dilation was restored by albumin. Conclusions. LPC affects several pathways that inhibit vasodilation, all of which are salvaged by addition of albumin.