Hypertensive activity of synthesized PTH(25-34) and Ac-PTH(25-30)-NH2 in rats

Parathyroid hormone (PTH) is secreted by parathyroid glands and is the main known factor that control plasma calcium concentration. There are many indications that PTH or products of PTH degradation influence the mean arterial blood pressure (MAP). These observations might be important in diseases accompanied with the overproduction of PTH such as primary hyperparathyroidism (PHPT). It was shown that the six amino acids PTH precursor-PRO-PTH with reversed sequence (PRO-rs), which contains a rare tripeptide -Arg-Lys-Lys- fragment, induces significant hypertensive response in rats. This strong alkali tripeptide is also present in the position 25-27 of the PTH molecule. The aim of the present study was to synthesize, by the solid phase peptide synthesis method, PTH fragments including the -Arg-Lys-Lys- sequence and test their influence on blood pressure and calcium plasma concentration in rats. Our study demonstrated that PTH(25-34) and the acetylated amide analogue of PTH(25-30), (Ac-PTH(25-30)-NH(2)) were hypertensive in the physiological doses. The presence of strong alkali sequence -Arg-Lys-Lys- in PTH(25-30) fragment is not sufficient to induce hypertension either in physiological or pharmacological doses in rats. Therefore, both the proximity of the -Arg-Lys-Lys- sequence and length of the peptide might also play roles as pressure factors.