Proteinuria-associated endothelial dysfunction is strain dependent.
BACKGROUND
Proteinuria-associated endothelial dysfunction (ED) is assumed to play a main role in the cardiovascular morbidity in proteinuric patients. However, the connection between proteinuria and systemic endothelial function is not clear yet. Therefore, we studied aortic endothelial function in Munich Wistar Fromter (MWF) and fawn-hooded hypertensive (FHH) inbred rat strains with genetic proteinuria to determine the specific impact of proteinuria on the development of ED.


METHODS
Proteinuria, cardiac function, systemic blood pressure, plasma lipid profiles, aortic endothelial function, plasma levels of cyclo-oxygenase products and dimethylarginines were investigated in 26-week-old inbred rat strains with (MWF and FHH) and without [Lewis (LEW) rats] proteinuric renal disease.


RESULTS
The endothelium-dependent relaxation was significantly reduced in MWF (p < 0.05 vs. LEW or FHH). The plasma thromboxane B(2), prostaglandin F(2alpha) and prostaglandin E(2)levels were higher in MWF (p < 0.05 vs. LEW or FHH), whereas the 6-keto-prostaglandin F(1alpha) level was comparable in all groups. The arginine/asymmetric dimethylarginine ratio was highest in MWF.


CONCLUSIONS
This study differentiates common risk factors for ED in renal disease. Despite clear-cut proteinuria, FHH rats were devoid of changes in aortic endothelial function, indicating that some other deleterious factors must accompany proteinuria in order for ED to ensue. Further exploration of this model may serve to dissect mechanistical pathways and guide the development of protective strategies in the vascular damage of renal disease.
Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, The Netherlands. n.ulu@med.umcg.nl
Nadir
N
Ulu
Regien G
RG
Schoemaker
Robert H
RH
Henning
Hendrik
H
Buikema
Tom
T
Teerlink
Freek J
FJ
Zijlstra
Stephan J L
SJ
Bakker
Wiek H
WH
van Gilst
Gerjan
G
Navis
D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D011507:Proteinuria / Q000150:complications* / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains