The effects of parathyroid hormone (PTH) were examined in three model systems to determine the mechanism of PTH action in vascular tissue. Bovine parathyroid extract and synthetic bPTH-(1-34) relaxed norepinephrine-contracted rabbit aortic strips in a dose-dependent fashion. The ED50 was 33.1 nM (21.8-50.1 nM). The hypotensive diterpene, forskolin and the phosphodiesterase inhibitors, methylisobutylxanthine and papaverine, all greatly potentiated the relaxant action of PTH. Primary cultures of vascular smooth muscle cells isolated from rabbit and rat aorta and bovine pulmonary artery all responded to bPTH-(1-34) with 5- to 10-fold increases in intracellular cyclic AMP concentrations within 1 min. Again, this action of PTH was also markedly augmented (3-fold or greater) by methylisobutylxanthine, papaverine or forskolin. In addition, 1 microM bPTH-(1-34) stimulated adenylate cyclase activity in membrane preparations from vascular smooth muscle cells in the presence or absence of 100 microM GMPPNHP. These results indicate that PTH exerts direct relaxant actions on vascular smooth muscle and that cyclic AMP may be involved in the mechanism of PTH action in vascular tissue.
1-Methyl-3-isobutylxanthine Adenylyl Cyclases