Cardiovascular effects of H3 histamine receptor inverse agonist/ H4 histamine receptor agonist, clobenpropit, in hemorrhage-shocked rats

Hemorrhagic shock has a potential to be life-threatening when it is not treated. The main causes of hemorrhagic shock involve: (1) forces causing injury; and (2) diseases that can cause hemorrhage., Therefore, due to the causes of hemorrhagic shock and the life-threatening potential, the search for new methods of shock treatment is extremely valuable to the modern medicine. The aim of this study was to investigate the influence of clobenpropit in the model of hemorrhagic shock. The experiments were conducted in 110 adult male Wistar rats weighing between 205 and 470g. 1, 2 and 5 μmol/kg of intravenous H3 receptors reverse agonists, clobentropit, and/or 1, 5 and 10 μmol/kg H3 receptor agonist, imetit, were used as general anesthetics. Irreversible hemorrhagic shock was induced by the paused bleeding until the mean arterial pressure (MAP) lowered to the level of 20–25 mmHg. It was proved that, in cases of critical hypotension, clobenpropit triggered a dose-dependent increase of: systolic blood pressure (SBP), diastolic blood pressure (DBP), MPA and heart rate (HR) of rats with critical hypotension. The most significant changes in hemodynamic parameters were achieved by administrating dosages of 2 mmol/kg. This resulted in the survival rate increase to up to 100%. However, imetit did not trigger any hemodynamic changes nor an increase in SBP, DBP, MAP or HR. Furthermore, it was found that the premedication with prazosin, yohimbine, 6-hydroxydopamine and the vasopressin V1a receptor antagonist blocked the effects of clobenpropit. Additionally, premedication with propranolol, captopril and ZD 7155 did not cause any significant changes in the measured hemodynamic parameters. In conclusion, after an intravenous injection clobenpropit, the inverse agonist of H3 histamine receptors/agonist of histamine receptors H4, causes a resuscitating effect on rats in hemorrhagic shock. Moreover, such effect is based on the effector mechanisms of sympathetic nervous system and vasopressin.

[1]  S. Dunnett,et al.  Behavioural recovery on simple and complex tasks by means of cell replacement therapy in unilateral 6‐hydroxydopamine‐lesioned mice , 2013, The European journal of neuroscience.

[2]  S. Brimijoin,et al.  Roles of dopaminergic innervation of nucleus accumbens shell and dorsolateral caudate-putamen in cue-induced morphine seeking after prolonged abstinence and the underlying D1- and D2-like receptor mechanisms in rats , 2013, Journal of psychopharmacology.

[3]  Hongjoo J. Lee,et al.  The role of central amygdala dopamine in disengagement behavior. , 2013, Behavioral neuroscience.

[4]  Luca Spaccapelo,et al.  Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in rats , 2012, Regulatory Peptides.

[5]  R. Levi,et al.  Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart , 2012, Journal of Pharmacology and Experimental Therapeutics.

[6]  Y. Kitamura,et al.  Histamine H(3) receptor-mediated modulation of perivascular nerve transmission in rat mesenteric arteries. , 2011, European journal of pharmacology.

[7]  N. Nishiyama,et al.  Pretreatment with l-histidine produces a shift from methamphetamine-induced stereotypical biting to persistent locomotion in mice , 2010, Pharmacology Biochemistry and Behavior.

[8]  Ji-min Cao,et al.  Chemical sympathetic denervation, suppression of myocardial transient outward potassium current, and ventricular fibrillation in the rat. , 2008, Canadian journal of physiology and pharmacology.

[9]  J. Jochem Involvement of arginine vasopressin in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats , 2004, Inflammation Research.

[10]  J. Jochem Involvement of the renin-angiotensin system in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats. , 2004 .

[11]  R. Obuchowicz,et al.  Involvement of central and peripheral histamine H(3) receptors in the control of the vascular tone and oxygen uptake in the mesenteric circulation of the rat. , 2004, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[12]  J. Jochem Involvement of the sympathetic nervous system in the reversal of critical haemorrhagic hypotension by endogenous central histamine in rats , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[13]  J. Jochem Central histamine-induced reversal of critical haemorrhagic hypotension in rats--haemodynamic studies. , 2002, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[14]  Z. Chen Effect of clobenpropit on regional cerebral blood flow in rat hippocampus. , 2001, Acta Pharmacologica Sinica.

[15]  S. Guarini,et al.  Brain M3 muscarinic receptors are involved in the ACTH-induced reversal of hemorrhagic shock , 1990, Naunyn-Schmiedeberg's Archives of Pharmacology.

[16]  S. Guarini,et al.  The adrenocorticotropic hormone (ACTH)-induced reversal of hemorrhagic shock. , 1989, Resuscitation.

[17]  D. Jacobowitz,et al.  Pharmacological actions of 6-hydroxydopamine. , 1974, Pharmacological reviews.

[18]  Y. Kitamura,et al.  R-(-)-alpha-methylhistamine, a histamine H3 receptor agonist, induces endothelium-dependent vasodilation in rat mesenteric resistance arteries. , 2010, Biological & pharmaceutical bulletin.