title: Involvement of the histaminergic system in the resuscitating effect of centrally acting leptin in haemorrhagic shock in rats.
abstract: Leptin, acting centrally as a neuromodulator, induces the activation of the sympathetic nervous system, which may lead to a pressor action in normotensive animals. In haemorrhagic shock, leptin administered intracerebroventricularly (icv.) evokes the resuscitating effect, with long-lasting rises in mean arterial pressure (MAP) and heart rate (HR), subsequent increase in peripheral blood flows, and a 100% survival at 2 h. Since leptin is able to activate histaminergic neurons, and centrally acting histamine also induces the resuscitating effect with the activation of the sympathetic nervous system, in the present study, we investigated an involvement of the histaminergic system in leptin-evoked cardiovascular effects in haemorrhagic shock. The model of irreversible haemorrhagic shock, with MAP decreased to and stabilised at 20 - 25 mmHg, has been used. Leptin (20 μg) given icv. at 5 min of critical hypotension evoked 181.5% increase in extracellular hypothalamic histamine concentration during the first 10 min after injection. Rises in MAP, HR and renal, mesenteric and hindquarters blood flows induced by leptin were inhibited by icv. pre-treatment with histamine H1 receptor antagonist chlorpheniramine (50 nmol). In contrast, there was no effect of H2, H3 and H4 receptor antagonists ranitidine (25 nmol), VUF 5681 (25 nmol) and JNJ 10191584 (25 nmol), respectively. In conclusion, the histaminergic system is involved in centrally-acting leptin-induced resuscitating effect in haemorrhagic shock in rats.
authors.affiliation: Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland. jjochem@poczta.onet.pl.
authors.forename: J
authors.initials: J
authors.lastname: Jochem
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Altinbas
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Yalcin
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ottani
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Giuliani
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: V
authors.initials: V
authors.lastname: Savci
authors.affiliation: Chair and Clinical Department of Internal Diseases, Dermatology and Allergology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Zabrze, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kasperska-Zajac
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Guarini
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D018494:Histamine Agents / Q000494:pharmacology*; D007276:Injections, Intraventricular / Q000379:methods; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D018494:Histamine Agents; C506811:JNJ 10191584; D020738:Leptin; D002744:Chlorpheniramine; D006632:Histamine; D011899:Ranitidine