title: Adrenal dysfunction in portal hypertensive rats with acute hemorrhage.
abstract: Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the 'hepatoadrenal syndrome', but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down-regulation, suggesting the importance of adequate adrenocorticoid supplement in portal hypertension with hemorrhage and adrenal dysfunction.
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Affair and Planning, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Division of Digestive Therapeutic Endoscopy, Chang Gung Memorial Hospital, Taipei, Taiwan, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ming-Hung
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000150:complications*; D006975:Hypertension, Portal / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008236:Lypressin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077585:Terlipressin; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008236:Lypressin; D003907:Dexamethasone; D000077585:Terlipressin; D019001:Nitric Oxide Synthase; D003345:Corticosterone