17β-Estradiol Decreases Nitric Oxide Synthase II Synthesis in Vascular Smooth Muscle Cells*

Abstract

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.

Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro

“…Similar effects of progesterone on iNOS expression have been reported in various cell types with similar hormone concentrations (Miller et al . 1996; Zancan et al . 1999; Drew and Chavis 2000).…”

“…The completed reaction mixture was added to resin which binds positively charged [ 14 C]‐arginine substrate, and filtered through a column such that the resin was retained and the neutrally charged [ 14 C]‐citrulline flowed through, and could be quantified by means of liquid scintillation counting. The Griess reaction for nitrite detection was performed as described by Zancan et al . (1999).…”

Induction of hepatic inducible nitric oxide synthase by cholesterol in vivo and in vitro

“…These results suggested that pathway(s) other than NF-κB mediated the induction of iNOS expression by the high fat diet in liver tissues. There are several reports showing that estrogen may be a modulator of iNOS expression and activity, although the mechanism has yet been understood (Kauser et al, 1998;Zancan et al, 1999). It was obvious that the estrogen effects were not mediated by NF-κB, however, other possibilities are still open to discussion.…”

Androgen deprivation, estrogen treatment and vascular function in male rat aorta

“…Since the pattern of E 2 effects overlapped only to some extent in intact and castrated rats, interactions between estrogen and androgens are likely to be relevant in vivo. Despite the presence of estrogen receptors in males (Rubanyi et al 1997;Lindner et al 1998;Zancan et al 1999), it appears from recent studies that the lack of vasoprotection by estrogen in the male is dependent on the hormonal environment, i.e., the presence of testosterone (Oparil et al 1997). In addition, estrogen-independent activation of estrogen receptors may occur in vascular cells when serum estrogen concentrations are low ).…”