Angiotensin II in the Human Physiology: Novel Ways for Synthetic Compounds Utilization

Renin-angiotensin system (RAS) and its main product Angiotensin II (AngII) are in the focus of the pharmacological industry mainly because of hypertension treatment. Up-regulated RAS is generally associated with cardiovascular diseases and consequent organs injuries. The classic inhibition of RAS is based on the blocking of the type 1 AngII receptors and inhibition of ACE. The concept of the circulating and tissue RAS opens new challenges for the drug targeting. In spite of a big effort invested, in some cases a traditional RAS manipulation is struggling with unwanted side effects and/or resistance to treatment.

To improve the efficiency of the classic RAS inhibitors specific complications issuing from feed-back circuits inside the RAS have to be elucidated. Moreover, new peptidases identified in the AngII biosynthesis and Angiotensin 1-7/MAS pathways with opposing effects to AngII are tested for the clinical use. The aim of this review is also to bring attention to new tools in RAS manipulation based on the RNA interference (RNAi). RNAi employs small non-coding nucleic acids that interfere with the mRNA translation. The usefulness of this approach has been demonstrated in the treatment of oncological diseases and progress was also made in the field of the cardiovascular medicine.

We suppose that in the near future, in addition to traditional pharmacological tools, RNAi will contribute to the control of RAS and AngII production. RNAi may also be of importance in the manipulation of tissue RAS that is not easily accessible by the traditional chemical substances.