A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia

Abstract

Intermyocardiocytic fibrosis, i.e., nonreparative interstitial fibrosis with collagen fiber deposition, is commonly found in uremic patients and animals. The volume density of interstitial tissue in the left papillary muscle of uremic animals was found to be increased (from 1.9 +/- 0.7 to 4.2 +/- 1.1%; P < 0.001). The nuclei of interstitial cells, but not of endothelial cells, were enlarged, pointing to an activating signal that specifically acts on interstitial cells. Because of the known action of parathyroid hormone (PTH) on the heart, a potential role of PTH in the genesis of fibrosis was explored by comparing subtotally nephrectomized (NX) parathyroidectomized (PTX) rats receiving by osmotic minipump either saline or rat 1,34 PTH (100 ng/kg per hour dissolved in NaCl). Animals were on a standard 0.95% Ca diet. After PTX, they were switched to a high-calcium (3%) diet. At the end of the 14-day experiments, NX-PTX-PTH animals and NX-PTX-solvent animals were comparable with respect to mean body weight (335 versus 338 g), serum creatinine (1.2 versus 1.2 mg/dL), and serum-Ca (2.66 versus 2.63 mmol/L). The volume densities of cardiac interstitium were 4.71 +/- 0.87 versus 1.49 +/- 0.49, and those of capillaries were 8.07 +/- 1.54 versus 7.94 +/- 2.62, respectively (P < 0.001 by analysis of variance). Thus, PTX abolished and PTH restored intermyocardiocytic changes of experimental uremia. These observations argue for a permissive role of PTH for fibroblast activation and the genesis of the cardiac fibrosis of uremia.