The aim of this study was to investigate whether the inhibition of one of the endothelial receptor sites in the rat pulmonary artery (muscarinic, histaminergic, purinergic, a 2-adrenergic) affects the NO-mediated relaxation induced by the activation of the other type of receptors. Acetylcholine (ACh)-, histamine (Hist)-, adenosine (Ade)- , and clonidine (Clon)-induced endothelium-dependent relaxations were reduced by the administration of specific antagonists of muscarinic, H1-histaminergic, purinergic or a 2-adrenergic receptors, respectively. The inhibition of H1-histaminergic receptors by chlorphenyramine did not prevent ACh-induced relaxation. Similarly, the inhibition of muscarinic receptors by atropine did not prevent the relaxations to histamine, adenosine and clonidine. On the other hand, the relaxations induced by acetylcholine, histamine, adenosine or clonidine were regularly reduced by NO-synthase inhibitor NG-nitro-L-arginine methyl ester (10-4 mol/l). These results suggest that the inhibition of NO-synthase abolished arterial relaxations induced by all agonists. After inhibition of one type of the endothelial receptors, the NO-dependent relaxation could still be evoked by activation of one of the others., S. Kyselá, J. Török., and Obsahuje bibliografii
To assess the possible involvement of mast cells and/or their mediators in inflammatory bowel diseases, the effect of the histamine H1 antagonist Dithiaden was studied on a model of acetic acid-induced colitis in rats. Dithiaden pretreatment by intracolonic administration was found to reduce the extent of acute inflammatory colonic injury. This was manifested by a decrease in the score of gross mucosal injury, by lowered colonic wet weight and by diminished myeloperoxidase activity reflecting reduced leukocyte infiltration. Vascular permeability and gamma-glutamyl transpeptidase activity, elevated by acetic acid exposure, were decreased after Dithiaden pretreatment. The results indicate that locally administered Dithiaden may protect the colonic mucosa against an acute inflammatory attack by interfering with the action of the major mast cell mediator histamine., V. Nosáľová, O. Ondrejičková, J. Pečivová., and Obsahuje bibliografii
The purpose of this study was to determine the relaxant effects of acetylcholine after inhibition of vascular histaminergic receptors. In isolated rings of the rat pulmonary artery precontracted by phenylephrine (10~5 mol/1) both histamine (10-7 to 10-4 mol/1) and acetylcholine (10-8 to 3xl0-5 mol/1) produced concentration-dependent relaxations. The arterial relaxations induced by either histamine or acetylcholine were markedly reduced or abolished by administration of NO synthase inhibitor NG-nitro-L-arginine methyl ester (10“5 mol/1). Relaxant responses to histamine were not influenced by cimetidine, histamine H2-receptor antagonist, but were significantly decreased or abolished by treatment with chlorphenyramine or diphenhydramine, histamine Hi-receptor antagonists. On the other hand, chlorphenyramine and diphenhydramine did not prevent the appearance of endothelium-dependent relaxation to acetylcholine. The results suggest that relaxation to histamine in the rat pulmonary artery is mediated by Hi-histaminergic receptors and their inactivation docs not interfere with the endothelial capability to produce and/or release nitric oxide by the activation of other types of receptors.
The aim of this study was to determine the relative contribution of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in histamine-induced relaxation of isolated pulmonary artery from normotensive and hypertensive rats. The hypertension was induced by oral administration of NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME, 50 mg/kg/day) to normotensive rats for 8 weeks. In phenylephrine-precontracted arterial rings the histamine-induced relaxation was significantly reduced in L-NAME-treated rats compared to the controls. Indomethacin (cyclooxygenase inhibitor) and glibenclamide (ATP-sensitive K+-channel blocker) did not inhibit the relaxation response in either control or hypertensive rats. On the other hand, tetraethylammonium (TEA), a K+-channel blocker with a broad specificity, significantly reduced histamine-induced relaxation in the pulmonary artery from both groups examined. The TEA-resistant relaxation was completely abolished by additional administration of L-NAME to the incubation medium. The results indicate that histamine-induced relaxation of the pulmonary artery in both normotensive and hypertensive rats is mediated mainly by nitric oxide, whereas EDHF seems to play a minor role., J. Török., and Obsahuje bibliografii
The aim of this study was to evaluate the role of endogenous histamine in the regulation of reactive hyperaemia (RH) and coronary autoregulation in isolated rat hearts. The basal release of cardiac histamine (perfusion pressure 60 cm H2O) amounted to 100-200 pmol/min/g wL During the first 15 s following 30 s of coronary occlusion, the release of histamine increased about three times and returned to basal levels after approximately 90 s, paralleling the changes of coronary flow (CF). Blockade of Hi-receptors increased basal CF by 23±2 %, significantly reduced blood flow debt and prolonged the duration of RH. Blockade of H2- and H3-receptors produced a significant decline of CF, decreased RH flow and diminished RH by 40±3 %. Blockade of all three classes of histamine receptors indicated that endogenous histamine exerts predominantly vasodilatory effects (mediated by H2- and H3-receptors) on coronary circulation. Histamine-induced vasodilation appears to be NO-dependenL Changes of coronary perfusion pressure from 20 to 120 cm H2O were accompanied by an almost linear decrease of histamine release from about 200 to 40-50 pmol/min/g wL Blockade of histamine receptors decreased, while L-NAME significantly widened the autoregulatory range of the isolated rat heart, reduced CF and release of NO, but reversed the pattern of histamine release leaving the autoregulatory range unaltered, which indicate that endogenous histamine does not play a role in the regulation of coronary autoregulation.
We have evaluated whether the addition of either bradykinin or histamine favours the lymphatic absorption of human recombinant ¡nterferon-a2 (IFN-cq) administered by the subcutaneous route. Subcutaneous administration of IFN-a2 with bradykinin enhances IFN absorption via both capillaries and lymphatics, so that either the plasma or lymph areas under the concentration curves (ACJC) increase significantly up to 1751 ±483 and 1319±608 l(_l/ml/min respectively as compared to the respective ACJC values (613±208 and 483±213 ICJ/ml/min) obtained after IFN injection in normal saline. Since the lymph ACJC/plasma ACJC ratios remain unaltered, there is no preferential lymphatic absorption of IFN-a2 after bradykinin administration. Dual-label experiments, 125l-IFN-a2 in saline and 131l-IFN-a2 in saline containing 200 jig histamine were injected subcutaneously into the left and into the right shank of the same animal, gave similar results. The kinetics of 125l and 131l acid-soluble radioactivity confirm that histamine favours both plasmatic and lymphatic absorption.