Endothelium-derived vasoconstrictor prostanoids modulate
contractions to acetylcholine and angiotensin ii in mesenteric
resistance arteries of ren-2 transgenic rats.
Noll, Georg, Markus Lang, Marcel R. Tschudi, Detlev Ganten, Thomas F.
L[umlaut]uscher.
Cardiology, Cardiovascular Research, University Hospital Bern,
Switzerland, and Max Delbr[umlaut]uck Center for Molecular Medicine,
Berlin-Buch, Germany
APStracts 3:0412H, 1996.
We investigated vascular function in mouse Ren-2 transgenic rats with
hypertension. Mesenteric resistance arteries of transgenic and
Sprague Dawley rats (controls) were isolated at age 6 and 12 weeks
and suspended in myographs for isometric tension recording. Systolic
blood pressure was higher in transgenic than control rats
(p<0.05). Contractions to norepinephrine and endothelin-1 were
comparable in transgenic and control rats, but the sensitivity
decreased with age in both strains (p<0.05). At the age of 6
weeks contractions to angiotensin I were comparable in transgenics
and controls, but at 12 weeks of age the response to angiotensin I
was more pronounced in transgenics. The contractions to angiotensin
II were higher in transgenics and decreased with age in both strains.
Preincubation with the cyclooxygenase inhibitor meclofenamate or the
thromboxane receptor antagonist SQ 30741 blunted the response only in
6 weeks old transgenics. In quiescent vascular rings, acetylcholine
evoked endothelium-dependent contractions after inhibition of nitric
oxide formation by Nw-nitro-L-arginine-methylester (L-NAME) only in
transgenics. These contractions were inhibited by SQ 30741
(p<0.05), but not by the thromboxane synthase inhibitor CGS
13080. Contractions to the thromboxane analogue U 46619 were
comparable in both strains at the age of 6 weeks; at 12 weeks, the
sensitivity was increased in transgenic rats. (p<0.05). In
conclusion, in mesenteric resistance arteries of Ren-2 transgenic
rats (1) contractions to angiotensin I and II but not those to
norepinephrine and endothelin-1 are increased, (2) acetylcholine as
well as angiotensin II modulate endothelium-dependent contractions
mediated by prostaglandin H2. These alterations together with the
increased sensitivity to thromboxane could contribute to the
maintenance as well as to impaired tissue perfusion of this form of
hypertension.
Received 5 July 1995; accepted in final form 31 July 1996.
APS Manuscript Number H608-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996