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Abstract: Haemorrhagic shock is a life threatening condition, and, as such, it is important to understand the mechanisms taking part in its reversal. In the 1990s, it was shown that activation of serotonin 1A receptors is responsible for the circulatory decompensation and development of the sympathoinhibitory phase. In previous reports, it was demonstrated that activation of serotonin 1A receptors induces resuscitative effects in haemorrhaged rats. However, the effectory mechanisms still require further investigation. The aim of the present study was to determine whether the sympathetic nervous system participates in the effects of serotonin through central serotonin 1A receptors in haemorrhagic shock in rats. In order to determine the role of the sympathetic nervous system alpha-1-, alpha-2-, and beta-adrenergic receptor agonists – prazosin, yohimbine and propranolol, respectively, were used. We found that stimulation of the central serotonin 1A receptors by the administration of a selective agonist – 8-hydroxy-2-(di-n-propylamino)tetralin, 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (8-OH-DPAT) into the lateral brain ventricle is connected with the activation of compensation mechanisms leading to the increase in the heart rate and blood pressure. The current results demonstrate that the stimulation of peripheral alpha-1-, alpha-2- and beta-adrenergic receptors plays an essential role in the resuscitative effect triggered by the stimulation of central serotonin 1A receptors. [Copyright &y& Elsevier]

Abstract: It has been found that dinitrosyl iron complexes with glutathione (DNIC-GS) injected into the blood flow of rats at a dose of 0.05μmoles/kg prior to hemorrhage significantly improve cardiac function under conditions of hemorrhagic shock manifested in increased stroke volume, left ventricular work and cardiac output to a level exceeding control values 1.5-fold. Enhanced myocardial contractile activity leads to a situation where mean arterial pressure does not decrease further despite the significant decrease of total peripheral resistance. The decrease of total peripheral vascular resistance of the vascular system under vasodilating effects of DNIC-GS used as nitric oxide donors improves microcirculation in experimental rats judging from increased rates of blood flow and low degree of erythrocyte aggregation. Pretreatment of rats with the complexes significantly increases survival (by 21%) under conditions of hemorrhagic shock. It is suggested that beneficial effects of DNIC-GS on systemic circulation parameters under conditions of hemorrhagic shock are determined by their antioxidant activity and the ability to induce S-nitrosylation of proteins. [Copyright &y& Elsevier]

Abstract: The present study investigated the mediated effect of protein kinase C (PKC) in arginine vasopressin (AVP)-induced restoration of vascular responsiveness and calcium sensitization following hemorrhagic shock. Using both isolated superior mesenteric artery from hemorrhagic shock rats and hypoxia-treated vascular smooth muscle cell (VSMC), we investigated the roles of PKC-α, δ and ε isoforms in AVP-induced restoration of vascular reactivity and calcium sensitivity. Meanwhile, effects of their specific inhibitors on the activity of myosin light chain phosphatase (MLCP), myosin light chain kinase (MLCK), and the phosphorylation of myosin light chain (MLC20) in VSMC were observed. The results indicated that AVP improved the reactivity of superior mesenteric artery and VSMC to norepinephrine and calcium following hemorrhagic shock and hypoxia. PKC-α inhibitor and PKC-ε inhibitory peptide antagonized these effects of AVP, while PKC-δ inhibitor only partially antagonized these effects of AVP. AVP up-regulated the expression of PKC-α and ε in the particulate fractions of hypoxia-treated VSMC with the decrease of the activity of MLCP and the increase of the phosphorylation of MLC20. These effects of AVP were inhibited by PKC-α inhibitor and PKC-ε inhibitory peptide, but not by the PKC-δ inhibitor. The results suggested that PKC plays an important role in AVP-induced restoration of vascular reactivity and calcium sensitivity following hemorrhagic shock. PKC-α and ε may be the main isoforms involved in this process and play effect via MLC20 phosphorylation dependent mechanism, while PKC-δ may be partially involved in AVP action by other mechanisms. [Copyright &y& Elsevier]