Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

[1]  S. Chiba,et al.  Evidence for the existence of postsynaptic beta-1 and beta-2 adrenoceptors in isolated simian facial veins , 2005, Heart and Vessels.

[2]  R. de Franchis Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. , 2005, Journal of hepatology.

[3]  G. Serafini,et al.  [Endoscopic treatment combined with adrenaline injection and coagulation with argon plasma in gastroduodenal peptic ulcer bleeding]. , 2001, Annali italiani di chirurgia.

[4]  Prabhat Kumar Sharma,et al.  The haemodynamic response to propranolol in cirrhosis with arterial hypertension: a comparative analysis with normotensive cirrhotic patients , 2010, Alimentary pharmacology & therapeutics.

[5]  S. Wang,et al.  EPINEPHRINE PROTECTS AGAINST SEVERE ACUTE GASTRIC BlEEDING IN RATS: ROLE OF NITRIC OXIDE AND GLUTATHIONE , 2005, Shock.

[6]  D. Landry,et al.  The pathogenesis of vasodilatory shock. , 2001, The New England journal of medicine.

[7]  D. Landry,et al.  The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. , 1992, The Journal of clinical investigation.

[8]  C. Thiemermann,et al.  Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Guth,et al.  Vasoactive agents and the gastric microcirculation. , 1974, Microvascular research.

[10]  J. Ward,et al.  Hemorrhage-Induced Vascular Hyporeactivity to Norepinephrine in Select Vasculatures of Rats and the Roles of Nitric Oxide and Endothelin , 2003, Shock.

[11]  S. Szabó,et al.  A quantitative method for assessing the extent of experimental gastric erosions and ulcers. , 1985, Journal of pharmacological methods.

[12]  J. Brayden Functional Roles Of KATP Channels In Vascular Smooth Muscle , 2002, Clinical and experimental pharmacology & physiology.

[13]  Xueji Zhang,et al.  Measurement of Nitric Oxide Production in Biological Systems by Using Griess Reaction Assay , 2003 .

[14]  Y. G. Wang,et al.  beta-Adrenergic stimulation induces acetylcholine to activate ATP-sensitive K+ current in cat atrial myocytes. , 1995, Circulation research.

[15]  M. Cappell Therapeutic endoscopy for acute upper gastrointestinal bleeding , 2010, Nature Reviews Gastroenterology &Hepatology.

[16]  T. Billiar,et al.  Novel roles of nitric oxide in hemorrhagic shock. , 1999, Shock.

[17]  Kunhong Xiao,et al.  A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1 , 2011, Nature.

[18]  R. Groszmann,et al.  Effect of selective blockade of beta 2-adrenergic receptors on portal and systemic hemodynamics in a portal hypertensive rat model. , 1985, Gastroenterology.

[19]  T. Bentley,et al.  Hemorrhagic Shock in Swine: Nitric Oxide and Potassium Sensitive Adenosine Triphosphate Channel Activation , 2004, Anesthesiology.

[20]  M. Nelson,et al.  Physiological roles and properties of potassium channels in arterial smooth muscle. , 1995, The American journal of physiology.

[21]  L. Gavrilović,et al.  Modulation of catecholamine-synthesizing enzymes in adrenal medulla and stellate ganglia by treadmill exercise of stressed rats , 2012, European Journal of Applied Physiology.

[22]  W. Wassef Upper gastrointestinal bleeding , 2004, Current opinion in gastroenterology.

[23]  W. Bilker,et al.  Hospitalization and mortality rates from peptic ulcer disease and GI bleeding in the 1990s: relationship to sales of nonsteroidal anti-inflammatory drugs and acid suppression medications , 2002, American Journal of Gastroenterology.

[24]  S. Chung,et al.  Effect of submucosal epinephrine injection on local gastric blood flow , 1990, Digestive Diseases and Sciences.

[25]  S. Gardiner,et al.  Effects of NG‐nitro‐l‐arginine methyl ester on vasodilator responses to acetylcholine, 5′‐N‐ethylcarboxamidoadenosine or salbutamol in conscious rats , 1991, British journal of pharmacology.

[26]  P. Timmermans,et al.  Extrasynaptic location of alpha-2 and noninnervated beta-2 adrenoceptors in the vascular system of the pithed normotensive rat. , 1982, The Journal of pharmacology and experimental therapeutics.

[27]  T. Kovacs Management of upper gastrointestinal bleeding , 2008, Current gastroenterology reports.

[28]  J. Ritter,et al.  Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by beta-adrenergic agonists in human forearm. , 1997, Circulation.

[29]  K. Broadley,et al.  A physiological basis for subclassifying beta‐adrenoceptors examined by chemical sympathectomy of guinea‐pigs. , 1986, The Journal of physiology.

[30]  Valery V. Tuchin,et al.  Endoscopic laser Doppler flowmetry in the experiment and in the bleeding gastric and duodenal ulcer clinic , 2007, Saratov Fall Meeting.

[31]  M. Cappell,et al.  Acute nonvariceal upper gastrointestinal bleeding: endoscopic diagnosis and therapy. , 2008, The Medical clinics of North America.

[32]  J. Vincent,et al.  Hemodynamic Effects of Glibenclamide During Endotoxemia: Contrasting Findings In Vitro Versus In Vivo , 2003, Shock.