Hypoalbuminaemia enhances the renal vasoconstrictor effect of lysophosphatidylcholine.
BACKGROUND
Lysophosphatidylcholine (LPC) causes vascular dysfunction in vitro. Lipoprotein LPC is increased in hypoalbuminaemia. Albumin binds LPC and restores LPC-induced abnormalities. We hypothesized that in vivo LPC impairs blood flow more in hypoalbuminaemia than in normoalbuminaemia.


METHODS
Increasing concentrations of LPC were infused intra-renally in Nagase analbuminaemic rats (NAR) and Sprague-Dawley rats (controls).


RESULTS
Intra-renal LPC (0.1 micromol/min, 20 min) reduced renal blood flow (RBF) more (P < 0.01) in NAR (from 8.3 +/- 0.3 to 4.0 +/- 1.1) than in controls (from 7.7 +/- 0.7 to 5.8 +/- 0.5 ml/min/g kidney). Lysophosphatidylethanolamine had no effect. After stopping LPC, RBF recovery was delayed in NAR [median 90 (range: 70-90) vs 45 min (40-60), P < 0.01]. Intravenous bovine serum albumin (BSA) prevented LPC-induced vasoconstriction in both strains. Prolonging LPC for 60 min delayed recovery of RBF. In this setting, intra-renal BSA completely restored RBF in 75 min (30-90), while intra-renal saline over 75 min only resulted in 33 +/- 13% recovery (P < 0.01). Baseline renal LPC content was unchanged in NAR. However, intra-renal LPC infusion doubled renal LPC content in NAR, but had no effect in controls.


CONCLUSIONS
In NAR, baseline RBF and renal LPC content are normal. However, exposure of NAR to LPC results in much more vasoconstriction and accumulation of LPC than in normoalbuminaemia. Addition of albumin prevents and restores LPC-induced vasoconstriction.
Vuong
Thi Danh
TD
Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
Braam
Branko
B
Willekes-Koolschijn
Nel
N
Boer
Peter
P
Koomans
Hein A
HA
Joles
Jaap A
JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D034141:Hypoalbuminemia / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D008244:Lysophosphatidylcholines; D014662:Vasoconstrictor Agents