Effect of endothelin antagonism on blood pressure and vascular
structure in renovascular hypertensive rats.
Li, Jin-S., Laurent Knafo, Andr[acute]e Turgeon, Ra[acute]ul Garcia,
Ernesto L. Schiffrin.
MRC Multidisciplinary Research Group on Hypertension, Clinical
Research Institute of Montr[acute]eal, University of Montr[acute]eal,
Montr[acute]eal, Qu[acute]ebec, Canada
APStracts 3:0019H, 1996.
In order to investigate the potential pathogenic role of endothelin in
blood pressure elevation and vascular hypertrophy in renovascular
hypertensive rats, which present 2-fold elevations in endothelin-1
mRNA abundance in blood vessels, the response of blood pressure and
vascular structure to chronic treatment with the endothelin receptor
antagonist bosentan was evaluated. One-kidney one clip (1-K 1C) and
2-K 1C Goldblatt hypertensive rats were treated for two weeks with
bosentan 100 mg/Kg per day in their chow and systolic blood pressure
was measured by the tail-cuff method. Vascular structure was studied
in small arteries mounted on a wire-myograph. Treatment with bosentan
did not result in significant change in systolic blood pressure or in
the structure of small coronary, renal cortical, mesenteric or
femoral arteries in 1-K 1 C or in 2-K 1C hypertensive rats. In
conclusion, modest (2-fold) elevations of endothelin-1 gene
expression in blood vessels in renovascular hypertension are not
associated with hypotensive responses or regression of vascular
hypertrophy during treatment with endothelin antagonists, in contrast
to what is found in DOCA-salt hypertensive rats, which exhibit very
dramatic increases in endothelin-1 expression (5-8-fold) and do
respond to endothelin antagonism with blood pressure lowering and
regression of vascular hypertrophy. These small elevations of
vascular endothelin-1 gene expression thus do not appear to indicate
the presence of an endothelin component in blood pressure elevation
in renovascular hypertension in rats.
Received 30 October 1995; accepted in final form 14 December
1995.
APS Manuscript Number H1011-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96