BLOOD-PRESSURE-INDEPENDENT WALL THICKENING OF INTRAMYOCARDIAL ARTERIOLES IN EXPERIMENTAL UREMIA - EVIDENCE FOR A PERMISSIVE ACTION OF PTH

Background. Abnormalities in cardiovascular structures, e.g. LV hypert rophy and thickening of vessels (arteries, arterioles, veins) are hall marks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the ge nesis of cardiac fibrosis. Purpose of the study. The present study in rats with experimental renal failure was designed to examine whether P TH was permissive for wall thickening of intramyocardial arterioles as well. Methods. Male SD rats were sham operated or subtotally nephrect omized and maintained for 2 weeks. Subgroups of subtotally nephrectomi zed (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PT H was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statist ically different between the groups. After perfusion fixation, intramy ocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). Results. In random samples of the left ventricle,wall thickness of ar terioles was 2.2+/-0.25 mu m in sham-op controls and 2.76+/-0.41 in SN X (n = at least 8 animals per group). SNX-PTX animals + solvent did no t differ significantly from sham-op controls (2.08+/-0.42 mu m), while SNX-PTX animals + PTH had values not significantly different from SNX (2.59+/-0.54 mu m). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110+/-13.3 mmHg, S NX 138+/-8.4 mmHg, SNX-PTX + solvent 142+/-5.2 mmHg; SNX-PTX + PTH 148 +/-5.7 mmHg). PTH treated animals showed signs of marked vascular smoo th-muscle cell and endothelial-cell activation. Conclusions. The data suggest that wall thickening of intramyocardial arterioles in short-te rm experimental uraemia is dependent upon the presence of PTH (permiss ive effect).