title: Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.
abstract: Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow. Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.affiliation: Department of Physiology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Magierowska
authors.affiliation: Department of Physiology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Magierowski
authors.affiliation: Department of Physiology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Ptak-Belowska
authors.affiliation: Department of Physiology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Pajdo
authors.affiliation: Department of Physiology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.affiliation: Department of Pharmacology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Olszanecki
authors.affiliation: Department of Pharmacology Jagiellonian University Medical College, Cracow. Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000502:physiology; D064426:Gasotransmitters / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D000809:Angiotensins; D064426:Gasotransmitters; D010455:Peptides; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D012083:Renin
keywords: Stress; angiotensin-(1-7); carbon monoxide; gastric blood flow; gastric lesion; ghrelin; hydrogen sulfide; orexin; oxidative stress; renin-angiotensin system