Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH

BACKGROUND.: Abnormalities in cardiovascular structures, e.g. LV hypertrophyand thickening of vessels (arteries, arterioles, veins) arehallmarks of renal failure. They are in part independent ofelevated blood pressure. Parathyroid hormone (PTH) has beenshown to affect cardiac function and has also been identifiedas a permissive factor in the genesis of cardiac fibrosis. PURPOSE OF THE STUDY.: The present study in rats with experimental renal failure wasdesigned to examine whether PTH was permissive for wall thickeningof intramyocardial arterioles as well. METHODS.: Male SD rats were sham operated or sub-totally nephrectomizedand maintained for 2 weeks. Subgroups of subtotally nephrectomized(SNX) rats were parathyroidectomized (PTX). Saline or rat 1,34 PTH was administered by osmotic minipump. Eucalcaemia wasmaintained in PTX animals by a high-calcium diet (3%). Serumcalcium was not statistically different between the groups.After perfusion fixation, intramyocardial arterioles were assessedusing stereological techniques (wall thickness; wall/lumen ratio;minimal lumen diameter; length density). RESULTS.: In random samples of the left ventricle, wall thickness of arterioleswas 2.2±0.25 µm in sham-op controls and 2.76±0.41in SNX (n=at least 8 animals per group). SNX-PTX animals+solventdid not differ significantly from sham-op controls (2.08±0.42µm), while SNX-PTX animals+PTH had values not significantlydifferent from SNX (2.59±0.54 µm). Differencesin wall thickness were not paralleled by differences in systolicblood pressure (sham-op 110±13.3 mmHg; SNX 138±8.4mmHg, SNX PTX+solvent 142±5.2 mmHg; SNX-PTX+PTH 148±5.7mmHg). PTH treated animals showed signs of marked vascular smooth-musclecell and endothelial-cell activation. CONCLUSIONS.: The data suggest that wall thickening of intramyocardial arteriolesin short-term experimental uraemia is dependent upon the presenceof PTH (permissive effect).