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Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
Address all correspondence and requests for reprints to: Lina Puglisi, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. E-mail: Lina.Puglisi{at}unimi.it
Several studies have provided evidence for a direct effect of
17ß-estradiol on vessel wall via interaction with the
constitutively expressed nitric oxide synthase (NOS) by endothelium.
The aim of the present study was to investigate the effect of
17ß-estradiol on inducible NOS (NOS II) in primary culture of smooth
muscle cells (SMC) from rat aorta. We here prove that 17ß-estradiol
decreases the content and activity of NOS II in SMC. This effect
appears to be the consequence of ER activation, because: 1) ER
and
ERß are expressed in rat aorta SMC grown in culture; 2) low
concentrations of hormone modulate NOS II activity; 3) the specific
ER
antagonist ICI182,780 completely blocks 17ß-estradiol effect.
On the other hand, progesterone is deprived of any effect on NOS II
content or activity, proving the specificity of 17ß-estradiol effect.
In addition, we show that 17ß-estradiol can counteract the increase
in NOS II activity following cytokine treatment. The observation could
indicate a novel mechanism for the protective effects exerted by these
hormones in cardiovascular diseases and atherosclerosis in particular.
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