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Bulletin of Experimental Biology and Medicine, Vol. 150, No. 1, 2010 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
Effect of NO Inhibitors on Hypovolemic Shock-Induced Hypotension
S. Ya. Proskurjakov, M. V. Filimonova, O. N. Borovaya, N. G. Kucherenko, A. I. Trishkina, L. V. Shteyn, V. G. Skvortsov, L. P. Ulyanova, L. I. Shevchenko, and Yu. G. Verkhovsky
Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 149, No. 7, pp. 23-27, July, 2010 Original article submitted January 12, 2009
In vivo effect of isothiourea derivatives on NO production was studied by the method of electron paramagnetic resonance spectroscopy with a spin trap. We evaluated the inuence of these compounds on hemodynamic parameters in anesthetized rats with hypovolemic shock. A correlation was found between the size of S,N-substituents in isothiourea derivatives (methyl, ethyl, and isopropyl) and NO inhibitory activity of compounds. The antihypotensive effect was more pronounced in compounds with high NO inhibitory activity containing the isopropyl radical.
Key Words: inhibitors of nitric oxide synthesis; in vivo electron paramagnetic resonance spectroscopy with a NO spin trap; isothiourea derivatives; hypovolemic shock; antihypotensive effect
Syndrome of arterial hypotension is an urgent medical and social problem. Blood pressure drop contributes to damage to target organs due their impaired perfusion. These changes determine poor prognosis of the disease [14]. A serious problem is arterial hypotension under shock conditions due to sepsis, blood loss, trauma, and some medical manipulations (e.g., hemodialysis and antitumor therapy). There is no general concept of this problem [7]. A small number of pharmaceutical agents with antihypotensive activity are used in medical practice [13]. Our previous studies showed that cyclic and linear isothiourea (ITU) derivatives exhibit antihypotensive properties during experimental septic shock [5,6].
Here we evaluated a relationship between chemical structure, NO inhibitory activity in vivo, and effect of new ITU derivatives on blood pressure, HR, and
respiratory rate in anesthetized rats with hypovolemic
shock.
MATERIALS AND METHODS
We studied biological activity of N-substituted derivatives of ITU. Experiments were performed with the following compounds (Medical Radiology Research Center): N-acetyl-S-isopropyl ITU hydrobromide (1); S-ethyl ITU diethyl phosphate (2); isopropyl ITU diisopropyl phosphate (3); N-acetyl-S-ethyl ITU hydro-bromide (4); methyl ITU dimethyl phosphate (5); and N-acetyl-S-methyl ITU hydroiodide (6).
The compounds were identied by element analysis, nuclear paramagnetic resonance spectroscopy, and chromatography.
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