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 hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks 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 genesis of cardiac fibrosis.


OBJECTIVE
The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well.


METHODS
Male SD rats were sham operated or subtotally nephrectomized and 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 was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial 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 arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 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 smooth-muscle cell and endothelial-cell activation.


CONCLUSIONS
The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).
Amann
K
K
Department Pathology, Ruperto Carola University Heidelberg, Germany.
Törnig
J
J
Flechtenmacher
C
C
Nabokov
A
A
Mall
G
G
Ritz
E
E
D000818:Animals; D001160:Arterioles / Q000473:pathology; D001794:Blood Pressure; D003331:Coronary Vessels / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology*; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000502:physiology*; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
D010281:Parathyroid Hormone