17Beta-estradiol decreases nitric oxide synthase II synthesis in vascular smooth muscle cells.
Several studies have provided evidence for a direct effect of 17beta-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 17beta-estradiol on inducible NOS (NOS II) in primary culture of smooth muscle cells (SMC) from rat aorta. We here prove that 17beta-estradiol decreases the content and activity of NOS II in SMC. This effect appears to be the consequence of ER activation, because: 1) ER alpha and ER beta are expressed in rat aorta SMC grown in culture; 2) low concentrations of hormone modulate NOS II activity; 3) the specific ER alpha antagonist ICI182,780 completely blocks 17beta-estradiol effect. On the other hand, progesterone is deprived of any effect on NOS II content or activity, proving the specificity of 17beta-estradiol effect. In addition, we show that 17beta-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.
Zancan
V
V
Institute of Pharmacological Sciences, University of Milan, Italy.
Santagati
S
S
Bolego
C
C
Vegeto
E
E
Maggi
A
A
Puglisi
L
L
D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D009573:Nitrites; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D011374:Progesterone; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat