Hypertension, Vol 14, 542-548, Copyright © 1989 by American Heart Association
T Koga, Y Takata, K Kobayashi, S Takishita, Y Yamashita and M Fujishima
This study was undertaken to compare age-related changes in endothelium-
dependent vascular responses in both hypertensive and normotensive rats.
Aorta from normotensive Wistar-Kyoto (WKY) rats and spontaneously
hypertensive rats (SHR) aged 4-6 weeks (young), 3-6 months (adult), and
12-25 months (old) were examined for relaxation to acetylcholine, adenosine
5'-triphosphate (ATP), and sodium nitroprusside. Rubbed (endothelium
denuded) aorta from all groups displayed neither relaxation nor contraction
to acetylcholine. Maximal relaxation responses to acetylcholine were
reduced progressively with increasing age in unrubbed aorta of both SHR and
WKY rats. In addition, acetylcholine caused not only dose-dependent
relaxations at lower concentrations but also increases in tension at higher
concentrations in unrubbed aorta of old WKY rats as well as adult and old
SHR. However, indomethacin completely inhibited the tension development. As
a result, aorta treated with indomethacin demonstrated similar
acetylcholine-induced, endothelium-dependent relaxations in all groups. The
thromboxane A2 synthetase inhibitor (E)-7-phenyl-7-(3-pyridyl)-6- heptanoic
acid (CV-4151) partially but significantly depressed the increases in
tension in aorta of old WKY rats. The degrees of endothelium-dependent
relaxations to ATP and endothelium-independent relaxations to sodium
nitroprusside were almost similar in all groups. These findings suggest
that the release of or vascular responsiveness to endothelium-derived
relaxing factor in the aorta is well maintained through senescence in both
strains and that, in the aorta of not only SHR but also old normotensive
WKY rats, the endothelium releases contracting factors that may be
thromboxane A2 and other vasoconstrictor prostanoids.
ARTICLES
Age and hypertension promote endothelium-dependent contractions to acetylcholine in the aorta of the rat
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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