Inflammation, malnutrition and vascular contraction in experimental chronic kidney disease

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.

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.

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).

The inflammatory state which affects vascular smooth muscle cells plays a key role in determining vascular contraction and resistant artery tone.