The cause of essential hypertension is unknown and the pathogenesis is far from being under-stood completely. In the framework of this thesis, some unknown substances with strong ef-fects on the vasoregulatory system were isolated, identified and characterised. The basis of the thesis were the changes of the chromatographic and mass-spectrometric methods during the last ten years, which offered the possibility to isolate and to identify un-known biomolecules, and to clarify hereby unknown pathogenetic mechanisms. In the first part of the thesis, diadenosine polyphosphates (with 3-6 phosphates) were isolated, identified and quantified from different tissues and body fluids like adrenal glands, heart and platelets and plasma by using these innovative chromatographic and mass-spectrometric methods. Moreover, a potent vasoconstrictive dinucleoside polyphosphate with a purine and pyrimidine base was isolated from supernatants of stimulated endothelial cells. The concen-tration of this uridine adenosine tetraphosphate (Up4A) in plasma is sufficient to affect the vascular tone. The second part of the thesis deals with the isolation and characterisation of hypertensive agents in chronic renal failure (CRF) patients. In the secretome of mononuclear leukocytes, both Angiotensin II (Ang II) and des[Asp1]-[Ala1]-Ang II (named as “Ang A”) were isolated. The ratio Ang A / Ang II was significantly increased in plasma of CRF patients. Furthermore, p-hydroxy-hippuric acid was identified as a potent inhibitor of the Ca2+-ATPase, and phenylacetic acid was described as an inhibitor of the inducible NO synthase (iNOS). Finally, the effects of different hemofiltration membranes on the filtration rate of some identified sub-stances were analysed. In summary, some unknown substances with strong effects on the vasoregulatory system were isolated, identified and characterised. The thesis corroborates the hypothesis that hypertension is a disease caused by many yet unknown different factors and regulatory systems. It is very likely that there are still many other unknown factors. The identification of each unknown fac-tor offers the possibility to develop new and more appropriate therapeutic approaches
