CARDIOVASCULAR ACTIONS OF PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE

Cardiovascular cells (cardiomyocytes and smooth muscle cells) are targ et cells for parathyroid hormone (PTH) and the structurally related pe ptide parathyroid hormone-related peptide (PTH-rP). PTH activates prot ein kinase C (PKC) of cardiomyocytes via a PKC activating domain previ ously identified on chondrocytes. Activation of PKC leads to hypertrop hic growth and re-expression of fetal type proteins in cardiomyocytes. This hypertrophic effect of PTH might contribute to left ventricular hypertrophy in hemodialysis patients with secondary hyperparathyroidis m. PTH-rP is expressed in cardiovascular cells (endothelial cells and smooth muscle cells). It does not mimic the above described actions of PTH but exerts effects of its own on cardiomyocytes. These effects in volve activation of protein kinase A, via a N-terminal domain distinct from that identified on PTH, and activation of PKC, via a C-terminall y located domain distinct from that found on PTH. On smooth muscle cel ls PTH and PTH-rP reduce the influence of extracellular calcium, throu gh cAMP-dependent mechanisms. These inhibitory effects on voltage-depe ndent L-type calcium channels of smooth muscle cells cause vasorelaxat ion. Present studies concerning cardiovascular actions of either PTH a nd PTH-rP suggest that increased plasma levels of PTH and PTH-rP influ ence cardiomyocyte and smooth muscle cell physiology. It can be assume d that PTH-rP acts as a paracrine or autocrine modulator in heart and vessels. (C) 1998 Elsevier Science B.V.