Laboratory Investigation

Kidney International (1981) 20, 173–180; doi:10.1038/ki.1981.119

Role of vasopressin in impaired water excretion in conscious rats with experimental cirrhosis

Stuart L Linas, Robert J Anderson, Stephen J Guggenheim, Gary L Robertson, Tomas Berl and with the technical assistance of David C Dickmann

Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, and Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois

Correspondence: Dr S L Linas, Medicine/Renal, Box C-281, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, USA

Received 7 July 1980; Revised 10 October 1980.

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Abstract

Role of vasopressin in impaired water excretion in conscious rats with experimental cirrhosis. The present study was undertaken to study the mechanism of impaired water excretion in experimental cirrhosis in the rat. Conscious rats in whom histologically proven cirrhosis was induced with carbon tetrachloride and phenobarbital were compared with control rats given phenobarbital alone. Impaired water excretion in experimental cirrhosis was verified by a basal hyponatremia (138 vs. 147 mEq/liter, P < 0.005) and an impaired excretion of water load (minimal urinary osmolality, 262 vs. 100 mOsm/kg; 58 vs. 102% of water load excreted, P < 0.001). To clarify the mechanism of this impaired water excretion, we measured glomerular filtration rate (GFR), renal blood flow (RBF), and vasopressin (VP) levels. In cirrhosis, GFR was normal but RBF was decreased (4.5 vs 6.8 ml/min/g, P < 0.01). VP levels were found to be higher in cirrhotic rats (1.61 vs. 0.71 pg/ml, P < 0.025). The significance of the impaired renal hemodynamics and the increase in VP was assessed by inducing cirrhosis in VP-free Brattle-boro (diabetes insipidus; DI) rats. Despite histologic, biochemical, and renal hemodynamic changes that were comparable to cirrhotic rats with an intact neurohypophysis, cirrhotic DI rats had no impairment in water excretion. To determine the cause of increased VP in experimental cirrhosis, we determined blood volume and systemic hemodynamics. Although plasma volume was greater in experimental cirrhosis (4.3 vs. 3.0 ml/100 g, P < 0.05), cirrhotic rats had a significantly lower peripheral resistance (0.37 vs. 0.42 mm Hg/ml/min/kg, P < 0.05) and mean arterial pressure (104 vs. 120 mm Hg, P < 0.001) than did control rats. These results document that experimental cirrhosis in the rat is associated with impaired renal water excretion in association with both abnormal renal hemodynamics and increased VP levels. The impaired water excretion, however, is solely VP mediated. The nonosmolar stimulus for VP release may be due to abnormal systemic hemodynamics.

Rôle de la vasopressine dans l'altération de l'excrétion de l'eau par le rat conscient atteint de cirrhose expérimentale. Cette étude a été entreprise pour élucider le mécanisme de l'altération de l'excrétion de l'eau au cours de la cirrhose du rat. Des rats conscients chez lesquels une cirrhose prouvée histologiquement a été induite par le tétrachlorure et le phénobarbital ont été comparés à des rats contrôles recevant seulement le phénobarbital. L'altération de l'excrétion de l'eau dans la cirrhose expérimentale a été vérifiée par l'hyponatrémie basale (138 vs. 147 mEq/litre, P < 0,005) et le défaut d'excrétion d'une charge en eau (osmolalité urinaire minimale 262 vs. 100 mOsm/kg; 58 vs. 102% de la charge d'eau sont excrétés, P < 0,001). Pour élucider le mécanisme de cette altération de l'excrétion de l'eau le débit de filtration glomérulaire (GFR), le débit sanguin rénal (RBF) et les concentrations de vasopressine (VP) ont été mesurés. Dans la cirrhose GFR est normal alors que RBF est diminué (4,5 vs. 6,8 ml/min/gm, P < 0,01). VP est plus élevée chez les rats cirrhotiques (1,61 vs. 0,71 pg/ml, P < 0,025). La signification des modifications de l'hémodynamique rénale et de l'augmentation de VP a été évaluée en créant des cirrhoses chez des rats sans VP de la souche Brattleboro (DI). Malgré des modifications histologiques, biochimiques et hémodynamiques rénales qui sont comparables à celles des rats dont la neurohypophyse est intacte, les rats DI cirrhotiques n'ont pas d'altération de l'excrétion de l'eau. Pour connaître la cause de l'augmentation de VP dans la cirrhose expérimentale le volume sanguin et l'hémodynamique systémique ont été étudiés. Quoique le volume plasmatique soit augmenté dans la cirrhose expérimentale (4,3 vs. 3,0 ml/100 g, P < 0,05) les rats cirrhotiques ont des résistances périphériques inférieures (0,37 vs. 0,42 mm Hg/ml/min/kg, P < 0,05) et une pression artérielle moyenne inférieure (104 vs. 120 mm Hg, P < 0,001) à celles des rats contrôles. Ces résultats indiquent que la cirrhose expérimentale du rat comporte une altération de l'excrétion de l'eau associée à une hémodynamique rénale anormale et à des concentrations de VP augmentées. L'altération de l'excrétion de l'eau, cependant, a la vasopressione comme seul médiateur. Le stimulus non osmolaire de la libération de VP pourrait être l'anomalie de l'hémodynamique systémique.

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