(Hypertension. 1997;29:435.)
© 1997 American Heart Association, Inc.
State-of-the-Art-Lecture |
Effects of Chronic ETA-Receptor Blockade in Angiotensin II-Induced Hypertension
From the Division of Cardiology, Cardiovascular Research, and Division of Hypertension, University Hospital, Bern; and the Division of Cardiology, University Hospital, Zürich, Switzerland.
Correspondence to Thomas F. Lüscher, MD, FESC, FACC, Cardiology, University Hospital, CH-8091 Zürich, Switzerland. E-mail 100771.1237{at}compuserve.com
Angiotensin II, a constrictor and mitogen of vascular smooth muscle cells, affects the release of endothelium-derived factors such as nitric oxide or endothelin-1. This study investigated the influence of endothelin-1, using the selective endothelin A receptor antagonist LU135252, on blood pressure and endothelial function in angiotensin II-induced hypertension in the rat. Two weeks of angiotensin II administration (200 ng/kg per minute) increased systolic blood pressure (+35±5 mm Hg; tail-cuff method) compared with placebo (P<.05). LU135252 alone did not affect systolic pressure but lowered the angiotensin II-induced pressure increase (P<.05). In isolated aortic rings, endothelium-dependent relaxations to acetylcholine were reduced in the angiotensin II group (P<.05 versus placebo) and improved by concomitant chronic LU135252 treatment (P<.05 versus angiotensin II). Blood pressure elevation strongly correlated with impaired endothelium-dependent relaxations to acetylcholine (r=-.967). LU135252 did not affect endothelium-independent relaxations to sodium nitroprusside, which were diminished after angiotensin II treatment (P<.05). In quiescent rings, chronic angiotensin II administration enhanced endothelium-dependent contractions to acetylcholine, which were reduced by LU135252 (P<.05). Impaired contractions to endothelin-1 and norepinephrine in the angiotensin II group were normalized after treatment with LU135252 (P<.05). Thus, chronic therapy with LU135252 partially prevents angiotensin II-induced hypertension and the alternations of the endothelial function observed in this experimental model.
Key Words: angiotensin II • endothelium • ET receptors • endothelins • LU135252 • aorta
Abbreviations: Ang II = angiotensin II • AT1 = type 1 angiotensin • AUC = area under the curve • ET-1 = endothelin-1 • ETA = endothelin subtype A • L-NAME = NG-nitro-L-arginine methyl ester • VSMC = vascular smooth muscle cells • WKY = Wistar-Kyoto
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