Article (Scientific journals)
Improvement of endothelial dysfunction by selective estrogen receptor-alpha stimulation in ovariectomized SHR.
Widder, Julian; Pelzer, Theo; von Poser-Klein, Christine et al.
2003In Hypertension, 42 (5), p. 991-6
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Keywords :
Animals; Aorta/enzymology/physiopathology; Cell Adhesion Molecules/chemistry/metabolism; Culture Techniques; Endothelium, Vascular/physiopathology; Estrogen Antagonists/pharmacology; Estrogen Receptor alpha; Female; Hypertension/metabolism/physiopathology; Microfilament Proteins; Nitric Oxide Synthase/metabolism; Nitric Oxide Synthase Type III; Ovariectomy; Phosphoproteins/chemistry/metabolism; Rats; Rats, Inbred SHR; Receptors, Estrogen/agonists; Serine/metabolism; Vasodilation
Abstract :
[en] Both known estrogen receptors, ERalpha and ERbeta, are expressed in blood vessels. To gain further insight into the role of ERalpha in a functional setting, we investigated the effect of the novel highly selective ERalpha agonist Cpd1471 on vascular reactivity in ovariectomized spontaneously hypertensive rats (SHR). After ovariectomy or sham operation, 12-week-old female SHR received either 17beta-estradiol (E2, 2 microg/kg body wt per day), the selective ERalpha agonist Cpd1471 (30 microg/kg body wt per day), or placebo. Acetylcholine-induced endothelium-dependent vasorelaxation was significantly blunted in aortas from ovariectomized rats (Rmax, 53%+/-3% versus sham, 79%+/-2%; P<0.001). Treatment with E2 or Cpd1471 significantly augmented acetylcholine-induced relaxation in ovariectomized rats (Rmax, 70%+/-2%; resp, 73%+/-2%). Endothelium-independent relaxation induced by sodium nitroprusside was not different among the four groups. The contractile response induced by the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine, an index of basal NO formation, was significantly lower in ovariectomized rats compared with sham-operated animals (53+/-2% versus 77%+/-5%; P<0.01) and was normalized by both E2 (70%+/-2%) and Cpd1471 (70%+/-3%). Aortic endothelial NO synthase (eNOS) expression and phosphorylation of the vasodilator-stimulated phosphoprotein, an index of NO/cGMP-signaling, was reduced in ovariectomized SHR and normalized by E2 and Cpd1471. In SHR after ovariectomy, endothelium-dependent NO-mediated vasorelaxation and eNOS expression are attenuated. The novel selective ERalpha agonist Cpd1471 prevented these pathophysiological changes to a similar extent as E2. Thus, the pharmacological principle of selective ERalpha activation mediates positive vascular effects.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Widder, Julian
Pelzer, Theo
von Poser-Klein, Christine
Hu, Kai
Jazbutyte, Virginija
Fritzemeier, Karl-Heinrich
Hegele-Hartung, Christa
Neyses, Ludwig ;  University of Luxembourg > Research Office
Bauersachs, Johann
Language :
English
Title :
Improvement of endothelial dysfunction by selective estrogen receptor-alpha stimulation in ovariectomized SHR.
Publication date :
2003
Journal title :
Hypertension
ISSN :
1524-4563
Publisher :
Lippincott Williams & Wilkins, Hagerstown, United States - Maryland
Volume :
42
Issue :
5
Pages :
991-6
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 16 October 2014

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