title: Stress-induced rise in endothelaemia, von Willebrand factor and hypothalamic-pituitary-adrenocortical axis activation is reduced by pretreatment with pentoxifylline.
abstract: Stress is considered to be a risk factor of several diseases. The following hypotheses were tested: (1) single exposure to an intensive stressor is followed by endothelial stimulation and/or damage to endothelial cells, (2) potential stress-induced endothelial cell damage is reduced by repeated pretreatment with pentoxifylline and (3) pentoxifylline treatment modifies neuroendocrine activation during stress reflected by changes in hypothalamic-pituitary-adrenocortical (HPA) axis function. Rats were treated with saline or pentoxifylline (20 mg/kg, s.c.) once daily for 7 days and then exposed to single immobilization stress for 20 or 120 min. In saline pretreated rats, stress exposure was followed by a rise in endothelaemia, von Willebrand factor concentrations, adrenocorticotropic hormone (ACTH) and corticosterone release, as well as by enhanced gene expression of hypothalamic corticotropin releasing factor (CRH). Stress-induced changes were reduced by pretreatment with pentoxifylline. Significant inhibition was observed in endothelaemia, plasma ACTH and corticosterone concentration in the adrenals. Thus, signs of endothelial injury as well as stress-induced hormone levels were reduced by pretreatment with pentoxifylline, although there is no evidence for a causal relationship. This protective action of pentoxifylline might be of benefit in the prevention and therapy of some stress-related disorders.
authors.affiliation: Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia. ueenjezo@savba.sk
authors.forename: D
authors.initials: D
authors.lastname: Jezova
authors.forename: V
authors.initials: V
authors.lastname: Kristova
authors.forename: J
authors.initials: J
authors.lastname: Slamova
authors.forename: M
authors.initials: M
authors.lastname: Mlynarik
authors.forename: Z
authors.initials: Z
authors.lastname: Pirnik
authors.forename: A
authors.initials: A
authors.lastname: Kiss
authors.forename: M
authors.initials: M
authors.lastname: Kriska
mesh_terms: D000311:Adrenal Glands / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D004334:Drug Administration Schedule; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007103:Immobilization; D007279:Injections, Subcutaneous; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects; D010431:Pentoxifylline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D010431:Pentoxifylline; D003345:Corticosterone