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(Hypertension. 1997;30:905-911.)
© 1997 American Heart Association, Inc.

Articles

Structure and Function of Small Arteries in Salt-Induced Hypertension

Effects of Chronic Endothelin-Subtype-A–Receptor Blockade

Livius V. d'Uscio; Matthias Barton; Sidney Shaw; Pierre Moreau; ; Thomas F. Lüscher

From the Division of Cardiology, Cardiovascular Research, and Division of Hypertension (S.S.), University Hospital, Bern, Institute of Physiology, University Zürich, and Division of Cardiology (T.F.L.), University Hospital, Zürich, (Switzerland).

Correspondence to Thomas F. Lüscher, MD, FACC, FESC, Professor and Head of Cardiology, University Hospital, CH-8091 Zürich, Switzerland. E-mail karluh{at}usz.unizh.ch

Abstract The involvement of endothelin in salt-induced hypertension is unclear. In the Dahl rat model, we studied the effects of a selective endothelin-subtype A (ET_A) receptor antagonist, LU135252, on blood pressure, vascular structure, and function. Dahl salt-sensitive and salt-resistant rats were treated for 8 weeks with 4% NaCl alone or in combination with LU135252 taken orally (60 mg/kg per day). The geometry and reactivity of basilar and mesenteric arteries were studied in vitro under perfused and pressurized conditions using a video dimension analyzer. Chronic salt administration increased systolic blood pressure by 37±3 mm Hg and media-lumen ratio of the basilar and mesenteric arteries in salt-sensitive rats (P<.05). These structural changes were caused by eutrophic remodeling in basilar and hypertrophic remodeling in mesenteric arteries. Endothelium-dependent relaxations to acetylcholine and contractions to endothelin-1 were impaired in mesenteric arteries of salt-sensitive rats on a high NaCl diet. LU135252 prevented part of the increase in systolic blood pressure and structural and functional alterations but increased plasma endothelin 1 levels (P<.05 versus salt-treated, salt-sensitive rats). LU135252 had no effect on these parameters in salt-resistant rats. These findings suggest that the long-term pressor effect of salt administration is mediated in part by the action of endogenous endothelin acting via ET_A receptors. Thus, chronic ET_A receptor blockade may be useful therapeutically to lower arterial pressure and prevent endothelial dysfunction and hypertrophic remodeling of resistance arteries in salt-sensitive forms of hypertension.

Key Words: basilar artery • mesenteric resistance artery • vascular remodeling • endothelin receptors • endothelium-derived relaxing factor • rats, Dahl

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