Abstract

Knowledge about the role of nitric oxide (NO) in physiological and pathological processes, such as blood vessels regulation, are widely used in experimental biology. Thus, the ability of inhibitors of NO synthase (NOS) to increase the blood pressure bypassing receptors can be claimed in the treatment of various hypotensive states. However, the problem of using the most of them in medicine is in its low selectivity and/or irreversible inhibition of synthase. We have synthesized several original reversible inhibitors selective to endothelial and inducible NOS and uncovered its expressed vasoconstrictive properties suitable for use in medical care and at the prehospital stage. Hemodynamic studies were carried out on male Wistar rats and dogs in hypotonic (the models of severe hemorrhagic shock, severe endotoxemia, ganglioplegic hypotension and refractory vazoplegia) and normotonic conditions. A single non-toxic (1/20 – 1/30 of LD16) injection of NOS inhibitor caused marked and prolonged increase in blood pressure without any negative effects. Our investigations suggest that the reversible selective NOS inhibitors are the new generation of promising vasopressors which can create new opportunities in emergency treatment of hypotension and critical states. This work is supported by Russian Ministry of Education and Science (Government Contract 14.N08.11.0078).