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Paracrine renal endothelin system in rats with liver cirrhosis
Author(s) -
Hocher Berthold,
Zart Rüdiger,
Diekmann Fritz,
Rohmeiss Peter,
Distler Armin,
Neumayer Hans H.,
Bauer Christian,
Gross Peter
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15390.x
Subject(s) - endocrinology , bosentan , medicine , endothelin receptor , kidney , renal cortex , renal function , renal medulla , cirrhosis , chemistry , receptor
1 Liver cirrhosis was induced in rats by CCl 4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal‐tissue endothelin‐1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non‐selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg −1 day −1 ) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2 Our study revealed an overexpression of the endothelin B receptor (ET B ) in the renal medulla of rats with liver cirrhosis (Cir: 2775 ± 299 fmol mg −1 ; Con:1695 ± 255 fmol mg −1 ; n = 8; means ± s.d., P < 0.01), whereas the density of ET B in the cortex and the endothelin A receptor (ET A ) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ET B in cirrhotic rats was due to an upregulation of ET B in the inner medullary collecting duct cells. 3 The tissue endothelin‐1 concentrations were increased in the renal medulla of cirrhotic rats (Cir:271 ± 68 pg g −1 wet wt.; Con: 153 ± 36 pg g −1 wet wt., n = 8; means ± s.d., P < 0.01). 4 The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 ± 0.62 ml day −1 , Cir + 6 mg kg −1 day −1 bosentan: 8.6 ± 1.0 ml day −1 ; Cir + 100 mg kg −1 day −1 bosentan:7.4 ± 0.6 ml day −1 ; n = 10; means ± s.e.mean). 5 We therefore suggest that the upregulation of the medullary ET B in cirrhotic rats is involved in the regulation of water excretion in rats with CCl 4 ‐induced liver cirrhosis.