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 contribute to increased risk of atherosclerosis in nephrotic syndrome. The addition of albumin reduces LPC in erythrocytes and endothelial cells. We hypothesized that the addition of albumin will salvage vasodilation in aortic rings previously exposed to LPC. LPC increases superoxide production and disturbs L-arginine availability. Therefore, we also decreased superoxide with a superoxide dismutase mimic, MnCl(2), and supplemented L-arginine in an attempt to restore vasodilation.


METHODS
Rat aorta rings, which had been incubated with various concentrations of LPC and human serum albumin (HSA), were mounted in organ chambers. Relaxation was studied with acetylcholine (0.01 to 100 micromol/L) after precontraction with phenylephrine (CON, 0.3 micromol/L; LPC, 0.03 micromol/L). In some studies MnCl(2) or L-arginine was added to the organ chamber.


RESULTS
LPC had time- and dose-dependent inhibitory effects on acetylcholine-mediated vasodilation, but no effect on nitroprusside-mediated vasodilation. Preincubation with albumin (50 or 6 g/L) could protect vasodilation against very high levels of LPC. After preincubation with LPC, the addition of albumin to the incubation salvaged vasodilation. Albumin was more effective after short LPC incubation. MnCl(2) had no specific effect on the LPC-mediated disturbance in vasodilation. L-arginine completely salvaged vasodilation at low concentrations of LPC. However, even high concentrations of L-arginine (1 mmol/L) could not improve vasodilation at LPC levels at which vasodilation was restored by albumin.


CONCLUSIONS
LPC affects several pathways that inhibit vasodilation, all of which are salvaged by addition of albumin.
Vuong
T D
TD
Nephrology and Hypertension, University Medical Center, Utrecht University, The Netherlands.
de Kimpe
S
S
de Roos
R
R
Rabelink
T J
TJ
Koomans
H A
HA
Joles
J A
JA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors; D008297:Male; D017895:Manganese Compounds / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D002712:Chlorides; D008244:Lysophosphatidylcholines; D017895:Manganese Compounds; D012709:Serum Albumin; D013481:Superoxides; D010656:Phenylephrine; D001120:Arginine; D000109:Acetylcholine; C025340:manganese chloride