title: Chronic glucocorticoid excess and impaired osmoregulation of vasopressin release in dogs with hepatic encephalopathy.
abstract: Chronic liver disease may be accompanied by disturbed sodium and water homeostasis. There is usually sodium retention and ascites. However, spontaneous natriuresis has also been reported in humans and experimental animals with liver cirrhosis. Chronic hypercortisolism, which may occur in dogs with advanced liver disease, is known to induce the inhibition of the osmostimulation of vasopressin (AVP) release. We have therefore investigated the osmoregulation of AVP release in 11 dogs with chronic hypercortisolism associated with advanced liver dysfunction and hepatic encepahlopathy and in 10 control dogs. Basal pituitary-adrenocortical activity was investigated by measuring the concentration in multiple plasma samples of adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and cortisol and the cortisol:creatinine ratio in 24-hr urine. Urine specific gravity was also measured. The feedback regulation of the system was investigated by measuring these hormones in plasma after an intravenous (iv) injection of 0.01 mg/kg of dexamethasone. The osmoregulation of the release of AVP was investigated by the intravenous infusion of a 20% NaCl solution at a flow rate of 0.03 ml/kg for 2 hr and the measurement of AVP in plasma sampled at 20-min intervals. The AVP release was analyzed in terms of the threshold osmolality at which it commenced and the sensitivity, which reflects the magnitude of the response. All dogs had highly increased urinary cortisol:creatinine ratios, ranging from 21 to 210 x 10(-6) (normally < 10 x 10(-6)). The mean basal plasma concentrations of the three pituitary-adrenocortical hormones were significantly increased. ACTH values were 35 to 146 ng/l (normally, 14 to 68), MSH values were 26 to 118 ng/l (normally, 10 to 36), and cortisol values were 88 to 194 nmol/l (normally, 23 to 112). The feedback inhibition of the secretion of ACTH and cortisol in response to dexamethasone was unaffected. Urine specific gravity was significantly decreased. The regulation of AVP release was found to be abnormal in all dogs with hepatic encephalopathy. The osmotic threshold at which the release of AVP was induced was abnormally high in seven of the dogs with liver disease and in the normal range in one. It could not be determined in three dogs. The sensitivity of AVP release in response to increasing plasma hypertonicity was normal in two dogs and decreased in nine. In three dogs, there was no increase in AVP release. None of the dogs had normal values for both the sensitivity and the threshold.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Rothuizen
authors.forename: W J
authors.initials: WJ
authors.lastname: Biewenga
authors.forename: J A
authors.initials: JA
authors.lastname: Mol
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000662:veterinary*; D006854:Hydrocortisone / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000097:blood; D009318:Natriuresis / Q000502:physiology; D009994:Osmolar Concentration; D010904:Pituitary Gland, Posterior / Q000378:metabolism / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D014667:Vasopressins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D006854:Hydrocortisone