Structure-cardiovascular activity relationships of parathyroid hormone

The effects of parathyroid hormone (PTH) analogues on isolated rat tail arteries and frog arteries and heart were examined. Synthetic bovine PTH fragment 1 to 34 [bPTH-(1-34)], porcine PTH-(1-34), [Ala1] pPTH-(1-34), and [Nle8] pPTH-(1-34) were tested for vasorelaxant activity on helical strips of the rat tail artery and the frog iliac and femoral artery, preconstricted with arginine vasopressin or arginine vasotocin in the rat and the frog, respectively. For cardiac activity, PTH analogues were administered to isolated frog atria, and atrial rate and atrial tension (AT) were measured. The N-terminal amino acid alanine appears to be pivotal for vasorelaxant activity of PTH molecules on the rat tail artery strips. Data from the frog preparations supported the finding in the rat, although the iliac and femoral arterial preparations differed in their responses. The N-terminal serine in pPTH-(1-34), compared with the other PTH analogues, appeared to be responsible for different cardiac responses, being negatively chronotropic and without effect on AT.