Expression of endothelins 1 and 3 in the rat kidney.
Firth, J D, K Schricker, P J Ratcliffe, A Kurtz.
Institute of Molecular Medicine, John Radcliffe Hospital,
Headington, Oxford OX3 9DU, England. 2: Physiologisches Institut der
Universitat Regensburg, Regensburg, Germany
APStracts 2:0078F, 1995.
Endothelins (ET's) 1 and 3 are expressed in the rat kidney, but the
factors which regulate this expression remain unknown. To try to
understand what these might be, we have measured the renal levels of
ET1 and ET3 mRNA's by the RNase protection assay technique after a
number of clearly defined renal / hemodynamic insults. (1) Six hours
after the induction of hemorrhagic anemia and hypotension there was a
3-fold increase in ET1 mRNA, and a simultaneous 3-fold decrease in
ET3 mRNA. This indicates that in this situation these two ET isoforms
are differentially controlled, and emphasises the need for assay
techniques capable of distinguishing between them. (2) One day after
application of an 0.2 mm clip to the left renal artery there was a
greater than 2.5-fold induction of ET1 mRNA in that kidney, which
persisted for ten days. A smaller rise in ET1 mRNA was seen in the
contralateral organ. After two days ET3 mRNA levels were reduced by
approximately 50% in the clipped organ. Both ramipril (an angiotensin
converting enzyme inhibitor; 7.5 mg/kg daily) and bosentan (a non
-selective endothelin receptor antagonist; 100 mg/kg daily)
substantially reduced the elevation in ET1 mRNA seen in the clipped
kidney after two days, suggesting that the generation of angiotensin
II and the action of ET itself are involved in the mechanism by which
clipping stimulates ET1 expression. By contrast, ramipril - but not
bosentan - prevented the reduction in ET3 mRNA levels. (3) Renal
denervation, dietary salt restriction or diuretic treatment
(furosemide) did not alter renal expression of ET1 or ET3. (4) ET2
mRNA was not detected in any sample from normal or experimental
kidney.
Received 10 January 1995; accepted in final form 14 April 1995.
APS Manuscript Number F5-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.