Inflammation, malnutrition and vascular contraction in experimental chronic kidney disease.
BACKGROUND
Inflammation is a well-defined factor influencing the development of cardiovascular complications in chronic renal failure. The aim of this study was to examine systemic inflammatory state defined by the level of serum haptoglobin, local inflammation defined by monocyte chemoattractant protein-1 (MCP-1) level and arterial response to phenylephrine in different stages of renal failure.


METHODS
Experiments were performed on male Wistar rats, weighing 290-380 g. The rats were divided into 4 groups: I (control) was shame-operated (n=12); II underwent 1/2 nephrectomy (n=12); III, 3/4 nephrectomy (n=8); IV 5/6 nephrectomy (n=12). After 4 weeks, blood pressure (BP) in carotid artery was measured, and blood was collected for blood urea nitrogen, creatinine, albumin, haptoglobin and MCP-1. We compared the smooth muscle contractility after stimulation of alpha1-adrenoreceptor with phenylephrine in all groups. The constriction of artery was measured as the increase in perfusion pressure at a constant flow of the perfusion fluid. Cumulative response curves (CRCs) were obtained using the van Rossum method.


RESULTS
We observed a significant shift of CRCs to the left in group III (calculated half-maximal contraction [EC50] was 1.55 x 10(-7) M/L vs. 7.71 x 10(-7) M/L in control) and a nonsignificant shift of CRCs to the left in group II (3.62 x 10(-7) M/L). Unexpectedly, rat tail arteries from the rats in the 5/6 nephrectomy group were characterized by diminished contraction response to phenylephrine (EC50 9.57 x 10-7 M/L). Systemic inflammation defined by haptoglobin level occurred in the 1/2 nephrectomy group and did not increase in more advanced stages of renal disease. Local inflammation (MCP-1 level) increased together with the renal failure progression. We found a positive correlation between MCP-1 level and haptoglobin only in the 5/6 nephrectomy group (r=0.65; p<0.01).


CONCLUSIONS
The inflammatory state which affects vascular smooth muscle cells plays a key role in determining vascular contraction and resistant artery tone.
Brymora
Andrzej
A
Department of Nephrology, Hypertension and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland. nerka@nerka.cpro.pl
Flisiński
Mariusz
M
Grześk
Grzegorz
G
Szadujkis-Szadurski
Leszek
L
Odrowaz-Sypniewska
Grazyna
G
Manitius
Jacek
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology*; D018932:Chemokine CCL2 / Q000097:blood; D004195:Disease Models, Animal; D006242:Haptoglobins / Q000032:analysis; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology; D008297:Male; D044342:Malnutrition; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018932:Chemokine CCL2; D006242:Haptoglobins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine